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Glucophage (metformin)

Where to purchase Metformin (don't take unless under a physician's supervision):

• Metformin at ReliableRX.

Related Topics:

• Actos (pioglitazone HCl) / Amaryl (glimepiride) / Avandia (rosiglitazone) / Byetta (exenatide) / Diabeta, Micronase (glyburide) /  Glucophage (metformin) / insulin / Januvia (sitagliptin) / Lantus (glargine) / Onglyza (saxagliptin) / Prandin™ (repaglinide) / Precose (acarbose) / Rezulin (troglitazone) / Starlix® (nateglinide) / Symlin (pramlintide acetate) / Victoza (liraglutide)

News & Research:

• Cross-link Breakers and Inhibitors - International Anti-Aging Systems - "metformin has a dual effect. It lowers blood glucose, (a well-known and established activity) plus, as new research is revealing, it is an effective inhibitor of cross-linking" - See metformin at ReliableRX.
• Metformin: The Most Effective Life Extension Drug is Also a Safe, Effective Weight Loss Drug - IAS Bulletin - "Metformin is also one of the most promising anti-aging, life extending drugs available"
• Glucophage (metformin) - rxlist.com - "With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease"
• Metabolic syndrome - CNN - "Doctors believe that the underlying cause of this cluster of risk factors is resistance to insulin ... Doctors use thiazolidinediones and metformin (Glucophage, Glucophage XR) to decrease insulin resistance in people with diabetes. These medications may help improve insulin metabolism in people with metabolic syndrome"
• Metformin (Glucophage) and bipolar - psycheducation.org - "In some cases this medication can decrease abdominal obesity ... Between 10 and 30% of people taking metformin have a decrease in their B12 levels ... this can show up is "anemia""
• Obesity and Fatty Liver disease - MedicineNet.com - "Doctors also are using medications to treat non alcoholic fatty liver disease. For example, insulin-sensitizing agents, such as the thiazolidinediones, pioglitazone (Actos) and rosiglitazone (Avandia), and metformin (Glucophage) not only help to control blood glucose in patients with diabetes, but they also improve enzyme levels in patients with non alcoholic fatty liver disease"
• Metformin Linked to Reduced Osteoarthritis Risk - Medscape, 4/24/23 - "Risk of osteoarthritis was 17% lower in patients taking metformin (95% confidence interval, –0.18 to 0.09), whose odds of osteoarthritis were approximately half the odds of those taking a sulfonylurea (OR, 0.5; 95% CI, 0.21-1.67). Risk of a total knee replacement was 10% lower in metformin users (95% CI, –0.28 to 0.08) with a similar reduction in odds, compared with those taking a sulfonylurea" - See metformin at ReliableRX.
• Metformin Linked With Less Dementia in People With Diabetes - Medscape, 7/28/22 - "In an observational study of more than 112,000 US residents aged 50 years or older with type 2 diabetes, new users of metformin had about a 20% lower rate of incident dementia compared to new users of sulfonylurea during 5 years of follow-up."
• Metformin Linked to Reductions in COVID-19 Viral Load - Medscape, 2/21/23 - "A total of 1323 patients in the study, enrolled at six centers, were randomized to treatment either with metformin 1000 mg per day on days 2 to 5 and 1500 mg per day on days 6 to 14 (n = 187), or to ivermectin 390-470 mcg/kg per day for 3 days (n = 187), fluvoxamine 50 mg twice daily for 14 days, and/or an exact-matching placebo in a 2 x 3 factorial trial design ... The mean rate of undetectable SARS-CoV-2 viral load at day 5 was 49.9% in the metformin group versus 54.6% in the placebo group (odds ratio [OR], 1.235), and the undetectable rate at day 10 was 14.3% in the metformin group and 22.6% in the placebo group" - See metformin at ReliableRX..
• Association of Metformin Use With Risk of Venous Thromboembolism in Adults With Type 2 Diabetes - Medscape, 6/14/22 - "Among 117,472 initiators of metformin and 13,835 initiators of sulfonylureas, 555 (1.3/1,000 person-years) and 75 (2.1/1,000 person-years) VTE cases occurred in each group, respectively. The multivariable-adjusted HR was 0.65 (95% CI: 0.51, 0.84). The corresponding risks for pulmonary embolism (adjusted HR = 0.71, 95% CI: 0.50, 1.01) and deep vein thrombosis (adjusted HR = 0.64, 95% CI: 0.48, 0.87) were also lower in metformin initiators than in sulfonylurea initiators"
• Early Metformin Minimizes Antipsychotic-Induced Weight Gain - Medscape, 6/1/22 - "The authors made a "strong" recommendation, for which there was moderate-quality evidence, that for patients for whom a lifestyle intervention is unacceptable or inappropriate, the use of metformin is an "alternative first-line intervention" for antipsychotic drug-induced weight gain ... Likewise, as a strong recommendation with moderate-quality evidence, the guidance encourages the use of metformin when nonpharmacologic intervention does not seem to be effective ... The guideline also says it is preferable to start metformin early for patients who gain more than 7% of their baseline weight within the first month of antipsychotic treatment. It also endorses metformin when weight gain is established ... The proposed starting dosage is 500 mg twice per day with meals, with increments of 500 mg every 1 to 2 weeks until reaching a target dose of 2000 mg/day ... The authors also recommend monitoring kidney function annually, as well as vitamin B12 levels and individual tolerability and compliance" - See metformin at ReliableRX.
• Metformin Use Likely Reduces Alzheimer's Disease Risk - Medscape, 4/21/22 - "Genetically proxied metformin use equivalent to a 6.75 mmol/mol (1.09%) reduction of A1c was associated with 4% lower odds of AD (P = 1.06 × 10-4) in individuals who did not have diabetes"
• Meta-Analysis Confirms Neuroprotective Benefit of Metformin - Medscape, 4/18/22 - "Pooled data showed that the relative risk (RR) associated with onset of neurodegenerative disease was 0.77 (95% CI, 0.67 - 0.88) for patients with diabetes taking metformin versus those not taking metformin ... The effect was greater with longer metformin use, with an RR of 0.29 (95% CI, 0.13 - 0.44) for those who took metformin for 4 years or more. Similarly, the studies conducted in Asian countries versus other locations suggested an added benefit for this population (RR, 0.69"
  • Neurodegenerative Disorders - utswmed - "Neurodegenerative disorders include: Alzheimer’s disease and other memory disorders ... Ataxia ... Huntington’s disease ... Parkinson’s disease ... Motor neuron disease ... Multiple system atrophy ... Progressive supranuclear palsy"
• Better Survival in Older Cancer Patients Who Also Take Metformin - Medscape, 4/12/22 - "Patients who took metformin versus those who did not had significantly better overall survival in both unadjusted (unadjusted hazard ratio [HR], 0.73; 95% CI, 0.69 - 0.76; P < .001) and adjusted models (adjusted HR, 0.77 ... the "underlying mechanisms of metformin related to cancer are still not completely understood," but many studies have shown metformin is associated with a reduction in the incidence of cancer, a reduction in cancer mortality, and an improvement in overall survival"
• Metformin Promotes the Hair-Inductive Activity of Three-Dimensional Aggregates of Epidermal and Dermal Cells Self-Assembled In Vitro - Skin Pharmacol Physiol 2021 Dec 9 - "These results suggest that metformin can promote hair follicle regeneration in vitro through up-regulation of the hair inductive capability of dermal cells"
• Metformin - New Longevity Research is Game Changing! - Dr Brad Stanfield, YouTube - He claims that metformin activates AMPK which decreased the benefits of exercise by 50%, therefore he only takes metformin for anti-aging on the days he doesn't exercise. Personally, I started taking 10 mg of empagliflozin and cut to metformin down to 500 mg after I exercise. The half-life of metformin is 6.5 hours so I don't see how that's going to be a problem 20 hours later. I exercise everyday so off days isn't an option. See empagliflozin inhousepharmacy.vu.
• Better Survival in Older Cancer Patients Who Also Take Metformin - Medscape, 4/12/22 - "Patients who took metformin versus those who did not had significantly better overall survival in both unadjusted (unadjusted hazard ratio [HR], 0.73; 95% CI, 0.69 - 0.76; P < .001) and adjusted models (adjusted HR, 0.77 ... the "underlying mechanisms of metformin related to cancer are still not completely understood," but many studies have shown metformin is associated with a reduction in the incidence of cancer, a reduction in cancer mortality, and an improvement in overall survival" - See metformin at ReliableRX.
• Metformin Benefits Patients Hospitalized for Heart Failure - Medscape, 12/14/21 - "SGLT2 inhibitors must be part of the treatment regimen for patients with heart failure of any type. This report supports also using metformin in those with type 2 diabetes and heart failure, but not in place of an SGLT2 inhibitor or to delay start of an SGLT2 inhibitor ... Patients started on metformin had a significant 19% reduction in 12-month incidence of all-cause death or HHF relative to other patients in the study in an analysis that adjusted for 29 potential confounders ... HHF was reduced by 20% in those who started metformin compared with those who did not ... A more granular analysis that divided patients by LVEF during their index hospitalization showed metformin use was linked with a significant 42% lower incidence of HHF and a significant 32% lower rate of HHF or all-cause death in patients with an LVEF of more than 40%"
• Metformin May Have Novel Role as Breast Cancer Drug - oncologystat.com - "In one recent hypothesis-generating metformin study, Dr. Josie M.M. Evans and coworkers at the University of Dundee (Scotland) evaluated roughly 11,876 patients with newly diagnosed type 2 diabetes, of whom 923 were subsequently diagnosed with cancer. The adjusted relative risk of malignancy in long-term metformin users was reduced by 44%, compared with nonusers ... In another population-based cohort study ... In another population-based cohort study, investigators at the Institute of Health Economics, Edmonton, Alta., identified 10,309 Saskatchewanians with type 2 diabetes. During an average of 5.4 years of follow-up after their diagnosis, 407 cancer-related deaths occurred. Cancer mortality was 3.5% in metformin users, 5.8% in insulin users, and 4.9% in individuals on sulfonylurea monotherapy. After adjustment in a multivariate Cox regression analysis, cancer-related mortality was 30% greater in sulfonylurea users than in metformin users. In insulin users, it was 90% higher than in metformin users"
• Common Diabetes Drug Shrinks Brain Tumors in Mice - Medscape, 11/3/21 - "Preliminary testing in mice suggests that the diabetes drug metformin might target these tumors specifically. The drug acts on cell processes that drive the growth of posterior fossa group A (PFA) ependymomas"
• Half Abandon Metformin Within a Year of Diabetes Diagnosis - Medscape, 8/3/21 - "One reason for the discontinuations, he said, is that patients might not realize they need to keep taking the medication ... "When a physician is seeing a person with newly diagnosed diabetes, I think it's important to remember that they might not know the implications of having a chronic condition. A lot of times we're quick to prescribe metformin and forget about it...Physicians might write a script for 3 months and three refills and not see the patient again for a year...We may need to keep a closer eye on these folks and have more regular follow-up, and make sure they're getting early diabetes education.""
• Metformin Use May Curb BCC Risk - Medscape, 7/15/21 - "In addition to general anticarcinogenic effects, metformin has also been shown to directly inhibit the sonic hedgehog pathway, a key pathway in basal cell carcinoma (BCC) pathogenesis ... Overall, metformin use was associated with a significantly lower risk of developing BCC, compared with nonuse (adjusted odds ratio, 0.71" - See metformin at ReliableRX.
• 'Remarkable' Response to Diabetes Drug in Resistant Bipolar Depression - Medscape, 6/7/21 - "The study needs replication, but this early clinical trial suggests that the mitigation of insulin resistance by metformin significantly improves depressive symptoms in a significant percentage of treatment resistant bipolar patients ... Patients were titrated up to 2000 mg of metformin, which was the full dose, over 2 weeks and then maintained on treatment for a further 24 weeks ... Those who reversed their insulin resistance showed a remarkable resolution in their depressive symptoms. The reduction in MADRS scores began at week 6, and were maintained through to the end of the study, and the Cohen's d effect size for MADRS depression scores for converters was 0.52 at week 14 and 0.55 at week 26 ... All had failed, on average, 8 or 9 trials in their lifetime. When they came to us, nothing else would work. That's one of the remarkable things about our results, just how well they responded when they had not responded to any other psychotropic medications"
• New benefits from anti-diabetic drug metformin - Science Daily, 4/15/21 - "the anti-diabetic drug metformin significantly prolongs the survival of mice in a model that simulates the pathology of non-diabetic chronic kidney disease (ND-CKD) by ameliorating pathological conditions like reduced kidney function, glomerular damage, inflammation and fibrosis. Metformin's mechanism is different from existing therapeutics which only treat symptoms, such as the blood pressure drug losartan, so the researchers believe that a combination of these medications at low dose will be highly beneficial. ... This research found that the appropriate combination of metformin and losartan significantly improved renal pathology and prolonged survival in a ND-CKD mouse model. This suggests that the old inexpensive drug metformin could become a new inexpensive drug for patients with chronic kidney disease" - See metformin and losartan at ReliableRX.
• Metformin Could Help Prevent Some Breast Cancers - WebMD, 2/1/21 - "Compared to women without diabetes, risk for estrogen-positive breast cancer was 38% lower among women with type 2 diabetes who had used metformin for 10 years or more ... Metformin can improve insulin sensitivity and correct high insulin levels by reducing the amount of insulin and insulin-like growth factor circulating in the body, which may activate cell signals involved in cancer ... Metformin may also slow breast cancer growth by activating an enzyme called adenosine monophosphate activated protein kinase (AMPK) ... It blocks a pathway involved in spread of cancer cells ... Metformin has been hailed as something of a miracle for many diseases other than diabetes. Some research has linked it to a longer life span, reduced risk of vision loss and improved fertility in men and women." - See metformin at ReliableRX.
• Metformin Treatment Again Linked to Fewer Deaths From COVID-19 - Medscape, 1/20/21 - "Notably, the reduction in mortality among those with diabetes taking metformin prior to COVID-19 diagnosis was significant: 11% of those patients died compared with 23% of those with diabetes not taking metformin"
• Metformin use reduces risk of death for patients with COVID-19 and diabetes, study finds - Science Daily, 1/14/21 - "Use of the diabetes drug metformin -- before a diagnosis of COVID-19 -- is associated with a threefold decrease in mortality in COVID-19 patients with Type 2 diabetes"
• Pilot Study Looks at Metformin in COVID-19 - Medscape, 12/7/20 - "A significant reduction in mortality was seen in women who had been taking metformin (defined as having at least 90 days of filled prescriptions) — an approximately 24% reduced likelihood of dying compared with similar women not taking the medication, after adjusting for confounding factors. There was no significant reduction in mortality among men, and the authors hypothesize that this may be due to a larger anti-inflammatory effect of metformin in women than in men."
• Metformin Improves Most Outcomes for T2D During Pregnancy - Medscape, 11/20/20 - "there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86) ... However, women in the metformin group had significantly less overall weight gain during pregnancy than those in the placebo group, at –1.8 kg (P < .0001) ... They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day ... Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or pre-eclampsia."
• Metformin Linked to Reduced Cognitive Decline, Dementia Risk - Medscape, 10/7/20 - "Over the 6 years of evaluation, the incidence of dementia among people with diabetes treated with metformin was 6% (four patients) versus 14.5% (eight patients) in those not treated with metformin and 8.2% (73 patients) among those with no diabetes ... The reduction in the incident dementia risk with metformin use compared with participants with diabetes not receiving metformin was 81% (HR, 0.19; P = .03) after adjusting for factors including age, sex, body mass index, heart disease, diabetes, stroke, hypertension, systolic blood pressure, smoking, non-English speaking, and APOEe4 genotype"
• Diabetes Drug Metformin May Protect Aging Brains - WebMD, 9/23/20 - "The study followed more than 1,000 people, aged 70 to 90, for six years ... Among the participants, 123 had diabetes and 67 were taking metformin ... People with diabetes who didn't take metformin had a five times higher risk of developing dementia during the study ... this isn't the first study to show that metformin might be linked to lower dementia risk. Other studies have found a similar association ... Metformin is an inexpensive drug and has few side effects" - See metformin at ReliableRX.
• Common diabetes drug reverses inflammation in the liver - Science Daily, 9/10/20 - "The diabetes drug metformin -- derived from a lilac plant that's been used medicinally for more than a thousand years -- has been prescribed to hundreds of millions of people worldwide as the frontline treatment for type 2 diabetes. Yet scientists don't fully understand how the drug is so effective at controlling blood glucose ... the new work showed that the same proteins, regulated by metformin, controlled aspects of inflammation in mice, something the drug has not typically been prescribed for ... metformin is currently entering clinical trials in the United States as a general anti-aging treatment because it is effects are so well established from millions of patients and its side effects are minimal ... Metformin and exercise elicit similar beneficial outcomes, and research has previously shown that AMPK helps mediate some of the positive effects of exercise on the body" - See metformin at ReliableRX.
• Does Metformin Reduce Risk for Death in COVID-19? - Medscape, 8/14/20 - "Scheen notes that several mechanisms have been proposed for the possible beneficial effect of metformin on COVID-19 outcomes, including direct improvements in glucose control, body weight, and insulin resistance; reduction in inflammation; inhibition of virus penetration via phosphorylation of ACE2; inhibition of an immune hyperactivation pathway; and neutrophil reduction ... Taken together, the four observational studies that Scheen reviews showed that metformin had a positive effect, with an overall 25% reduction in death (P < .00001), albeit with relatively high heterogeneity ... Because metformin is out of patent and very inexpensive, no pharmaceutical company is likely to be interested in planning a study to demonstrate the benefits of metformin on COVID-19-related clinical outcomes"
• Metformin Linked to Better Motor Function in Parkinson's - Medscape, 5/29/20 - "A small retrospective study showed that patients with PD and diabetes who took the antihyperglycemic agent performed significantly better on tests of motor and nonmotor function than their counterparts who did not ... compared with the patients not taking metformin, those taking the drug had a significantly better Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score (P = .04) and Benton Judgement of Line Orientation score, which assesses visuospatial function ... These patients also did significantly better on certain measures of cognitive impairment, including the Symbol Digit Modalities Test score (P = .03) and the Semantic Fluency total score (P = .003). A higher metformin cumulative dose was associated with the MDS-UPDRS rigidity score."
• Could Preoperative Metformin Improve Major-Surgery Outcomes? - Medscape, 4/17/20 - "The primary outcome, 90-day mortality, occurred in 3% of patients who received preoperative metformin and 5% of patients who did not ... Patients receiving metformin therefore had a 28% lower risk of death at 90 days (hazard ratio [HR], 0.72; 95% CI, 0.55 - 0.95; P = .02) ... Patients in both groups had the same rate of 30-day mortality (2%) ... However, 5-year mortality was lower in the group with, versus without, preoperative metformin, at 13% versus 17% (HR, 0.74; P < .001) ... The 30-day readmission rate was also lower in the preoperative metformin group than in the other group, at 11% versus 13% (HR, 0.84; P = .02) ... Similarly, the 90-day readmission rate was lower in the metformin group, at 20% versus 23% (HR, 0.86; P = .01) ... Preoperative inflammation was also lower in the patients with versus without preoperative metformin; the mean neutrophil to leukocyte ratio was 4.5 versus 5.0 (P < .001) ... These better outcomes in the metformin group were consistent across different types of surgeries"
• The Safety and Pharmacokinetics of Metformin in Patients With Chronic Liver Disease - Medscape, 4/6/20 - "The pharmacokinetics of metformin are not altered sufficiently in CLD patients to raise concerns regarding unsafe concentrations of metformin. There were no unsafe plasma lactate concentrations observed in CLD patients receiving metformin"
• Metformin May Be of Benefit, Even in Advancing Kidney Disease - Medscape, 4/2/20 - "In patients with advanced CKD, if metformin is used carefully while monitoring, it could be suggested as a treatment [for type 2 diabetes] that can slow the progress of kidney disease as well as [having a] cardiovascular benefit" - See metformin at ReliableRX.
• Cholesterol Drugs Might Help Curb Prostate Cancers - WebMD, 2/14/20 - "statins, taken alone or with metformin, did seem associated with an increase in survival ... Men who took both statins and metformin had higher median survival (3.9 years) than those who took statins alone (3.6 years), metformin alone (3.1 years), or those who did not take either drug (3.1 years)"
• Tackling Inflammation to Fight Age-Related Ailments - NYT, 12/23/19 - "Specialists in the biology of aging have identified a rarely recognized yet universal condition that is a major contributor to a wide range of common health-robbing ailments, from heart disease, diabetes and cancer to arthritis, depression and Alzheimer’s disease. That condition is chronic inflammation, a kind of low-grade irritant that can undermine the well-being of virtually every bodily system ... recent studies have identified measures potentially available to everyone that can minimize the potency of chronic inflammation and stymie — and possibly even reverse — its progression. The measures will come as no surprise to people familiar with the healthful advice that has been offered in this column for many years: Adopt a wholesome diet (details to follow), get regular exercise, avoid or reduce excess weight, get adequate quality sleep, minimize stress and don’t smoke ... As people age, their immune responses become less well regulated, resulting in elevated blood levels of inflammatory substances like C-reactive protein and chemokines, and allowing inflammatory agents like interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-alpha) to persist in body tissues ... The drug metformin, commonly used to treat Type 2 diabetes, is known to have an anti-inflammatory effect and will be tested for its ability to delay the development of age-related diseases in a forthcoming trial called TAME, the acronym for Targeting Aging with Metformin ... Another consequence of aging is the accumulation of so-called senescent cells, normal cells that stop dividing, contribute to tissue aging and secrete substances like cytokines that induce inflammation. Elimination of senescent cells can counter chronic inflammation, said Steven N. Austad, director of aging studies at the University of Alabama at Birmingham. A combination of two drugs, dasatinib and quercetin, was shown in a Mayo Clinic study in obese mice to remove senescent cells and permit cell growth to resume in the brain ... Dr. Hu recommends frequent consumption of foods known to have an anti-inflammatory effect. They include green leafy vegetables like spinach, kale and collards; fatty fish like salmon, mackerel, tuna and sardines; fruits like strawberries, blueberries, apples, grapes, oranges and cherries; nuts like almonds and walnuts; and olive oil. The recommended plant foods contain natural antioxidants and polyphenols, and the fish are rich in omega-3 fatty acids, all of which counter inflammation ... get regular dental cleanings to control periodontal disease, which can be a source of chronic inflammation ... be judicious in the use of antibiotics, antacids and nonsteroidal anti-inflammatory drugs (NSAIDs) that can disrupt the normally healthy population of microorganisms in the gut and result in “a leaky gut that lets bacteria into circulation and is very pro-inflammatory" - See quercetin at Amazon.com.
• Diabetes drug has unexpected, broad implications for healthy aging - Science Daily, 12/4/19 - "The results revealed that metformin turns on unexpected kinases and pathways, many independent of AMPK. Two of the activated kinases are called Protein Kinase D and MAPKAPK2. These kinases are poorly understood, but are known to have some relation to cellular stress, which could connect them to the health-span- and life-span-extending effects observed in other studies. In fact, metformin is currently being tested in multiple large-scale clinical trials as a health-span- and life-span-extending drug, but the mechanism for how metformin could affect health and aging has not been clear. The current study indicates that Protein Kinase D and MAPKAPK2 may be two players in providing these therapeutic effects, and identifies new targets and cellular processes regulated by AMPK that may also be critical to metformin's beneficial effects."
• Treatment of metabolic dysfunction could be a potential therapy for Alzheimer's disease - Science Daily, 10/17/19 - "metabolic defects occur well before any significant increase in the amount of amyloid-beta protein could be detected. The research used a tiny worm called Caenorhabditis elegans to identify these changes because it shares many similarities at the molecular level with human cells. A further breakthrough came when the team found that treatment of the worms with a common anti-diabetes drug called Metformin reversed these metabolic defects and normalised the worms' healthspan and lifespan"
• The Week That Wasn't: Reverse Aging, Lyme Test, Apple Health Studies - Medscape, 9/13/19 - "After a year of taking the recombinant human growth hormone dehydroepiandrosterone and metformin, men in a small clinical trial showed a decrease in scores of epigenetic age based on DNA methylation ... his is to our knowledge the first report of an increase, based on an epigenetic age estimator, in predicted human lifespan by means of a currently accessible aging intervention" - See Pure Encapulations 7-Keto DHEA at Amazon.com.
• Could Cheap Drug Metformin Prevent Dementia in Black Patients? - Medscape, 7/19/19 - "Over a mean follow-up of around 6.5 years, regardless of age, the African American participants showed a greater than 25% lower risk of dementia if they took metformin compared with a sulfonylurea (hazard ratio [HR], 0.73 ... In contrast, white patients had just a 4% to 8% lower risk (HR, 0.96 ... When stratified further by age group, in African Americans aged 50-64 years, dementia risk was reduced (HR, 0.60; 95% CI, 0.45 - 0.81). This effect was not seen among white patients in the same age group ... In the 65-74 years age bracket of white patients, there appeared to be a 10% lower risk of dementia on metformin compared with a sulfonylurea ... In African Americans of the same age, dementia risk was reduced by around 29% ... the drug could be working by reducing systemic inflammation"
• Diabetes drug alleviates anxiety in mice - Science Daily, 6/3/19 - "The antidiabetic medication metformin reduces anxiety-like behaviors in male mice by increasing serotonin availability in the brain ... the insulin-sensitizing drug metformin reduces levels of amino acids that impair the entry of tryptophan in the brain and thereby limit its conversion into serotonin. The drug's antidepressant-like effects were accompanied by improved neurotransmission in the hippocampus"
• Treatment With Metformin Is Associated With a Prolonged Survival in Patients With Hepatocellular Carcinoma - Medscape, 4/29/19 - "Treatment with metformin was associated with an improved survival in patients with T2DM and HCC. This effect was most pronounced in patients at potentially curative tumour stages"
• Metformin May Stop Weight Regain After Initial Loss - Medscape, 4/22/19 - "However, the newly reported data show that patients in the metformin group had greater long-term weight loss maintenance success ... During years 6 to 15 (after the intensive lifestyle counseling was completed and weight stabilized), weight loss relative to baseline was 6.2% (95% CI, 5.2% to 7.2%) in the metformin group, 3.7% (95% CI, 3.1% to 4.4%) in the intensive lifestyle group, and 2.8% (95% CI, 1.3% to 4.4%) in the placebo group — and 56%, 43%, and 42% of patients in these respective groups had kept off at least 5% of their initial weight."  - [Science Daily]
• Type 2 Diabetes Ups Odds of VTE, Metformin Reduces It - Medscape. 3/8/19 - "venous thromboembolism (VTE) ... is two to three times more common in patients with type 2 diabetes, compared with people with type 1, or those without diabetes ... The wonders of metformin just go on and on. It is a wonder drug ... Aspirin reduced odds of VTE, as expected, but interestingly metformin use also reduced the odds of VTE [approximately OR 0.92"
• Metformin and B12 Deficiency: A Bigger Problem Than We Thought - Medscape, 12/18/18 - "On average, the women were 63 years old, were taking 2000 mg/day of metformin, and had been on the drug for about 6 years ... The majority of the women had not had their B12 levels measured. However, upon testing, almost 1 in 10 were found to have a B12 deficiency." - See vitamin B12 at Amazon.com.
• Switching From Metformin to Sulfonylurea Raises CV Risks - Medscape, 7/18/18 - "Use of sulfonylureas as second-line treatment — whether by adding or switching — was associated with a significant 26% increased risk of myocardial infarction compared with continuing metformin monotherapy (incidence rate 7.8 vs 6.2 per 1000 patient-years; HR, 1.26) ... Sulfonylurea users also had a 28% greater risk for all-cause mortality compared with metformin monotherapy (27.3 vs 21.5 per 1000 patient-years; HR, 1.28) and a nearly eight-fold higher rate of severe hypoglycemia (5.5 vs 0.7 per 1000 patient-years; HR, 7.6)" - See metformin at the Antiaging Store.
• Metformin reverses established lung fibrosis - Science Daily, 7/3/18 - "Pulmonary fibrosis can develop after lung injuries like infections, radiation or chemotherapy, or it can have an unknown cause ... Interestingly, the drug that accelerated the resolution of lung fibrosis is metformin, which is a safe and widely used agent for non-insulin-dependent diabetes"
• Metformin Linked to Lower Mortality in Diabetes With Dementia - Medscape, 6/26/18 - "For older patients with both diabetes and dementia, taking metformin was associated with a reduction in all-cause mortality while insulin was associated with an increased risk for heart failure (HF) ... diabetic patients with dementia who take a dipeptidyl peptidase-4 inhibitor (DPP-4i) have a higher rate of myocardial infarction (MI) ... For all-cause mortality, metformin treatment was associated with a beneficial effect, with a hazard ratio (HR) of 0.83 ... On the other hand, risk for death was increased among insulin users (adjusted HR, 1.16"
• Common diabetes drug found safe for most diabetics with kidney disease - Science Daily, 6/5/18 - "there has been a longstanding concern in the medical community about prescribing metformin for people with both diabetes and CKD because it may cause lactic acidosis ... Lactic acidosis is a rare but serious complication, occurring when lactate -- a product of glucose breakdown -- builds up in the bloodstream, producing symptoms such as severe muscle pain, cramps, nausea and weakness. Because patients with CKD may be at increased risk of metformin-associated lactic acidosis, health care providers historically avoided prescribing metformin in this population ... Past studies show that metformin has multiple benefits beyond controlling blood sugar, including less weight gain, a lower risk of heart attack and even higher long-term survival than other medications that patients take to control blood sugar ... Overall, Grams and her colleagues found an association between metformin use and acidosis only in patients with severely decreased kidney function, defined as an eGFR of less than 30 mL/min/1.73 m2. A normal eGFR is considered to be over 90 mL/min/1.73 m2" - See metformin at the Antiaging Store.
• Common diabetes drug may also help with nicotine withdrawal - Science Daily, 4/5/18 - "investigators say metformin, an inexpensive drug commonly used to treat patients with type 2 diabetes, appears to block symptoms of nicotine withdrawal in rodents ... the research suggests that metformin, because of its long-term record of safety and relative lack of side effects, has "real potential" as a smoking cessation aid if clinical trials confirm the findings in mice" - See metformin at the Antiaging Store.
• FDA-approved high blood pressure drug extends life span in roundworms - Science Daily, 12/20/17 - "This is the first report of hydralazine treatment activating the NRF2/SKN-1 signaling pathway. We found the drug extends the life span of worms as well as or better than other potential anti-aging compounds such as curcumin and metformin"
  • Hydralazine - wikipedia.org - "Common side effects include headache and fast heart rate.[1] It is not recommended in people with coronary artery disease or in those with rheumatic heart disease that affects the mitral valve.[1] In those with kidney disease a low dose is recommended ... It was patented in 1949 ... The wholesale cost in the developing world is about 2.78 to 9.11 USD per month ... Hydralazine is not used as a primary drug for treating hypertension because it elicits a reflex sympathetic stimulation of the heart (the baroreceptor reflex).[8] The sympathetic stimulation may increase heart rate and cardiac output, and in people with coronary artery disease may cause angina pectoris or myocardial infarction.[9] Hydralazine may also increase plasma renin concentration, resulting in fluid retention ... Prolonged treatment may cause a syndrome similar to lupus which can become fatal if the symptoms are not noticed and drug treatment stopped"
• The Longevity Pill - Today.com, 9/8/17 - See the video.  I've been saying that about metformin since Moby-Dick was a minnow.
• Long-term Metformin May Reduce Coronary Calcium - Medscape, 5/30/17 - "The prevalence and severity of coronary artery calcium (CAC) after 14 years of metformin therapy were significantly lower in men, but not women, who started on the drug for prediabetes ... although it is "hard to be sure" why the metformin effect is lacking in women, previous studies have shown that metformin reduces testosterone levels in women but not in men. "Whether there's a metabolic difference between women and men that might count for a differential effect of metformin is a possibility, but we really don't know the answer.""
• Resveratrol preserves neuromuscular synapses, muscle fibers in aging mice - Science Daily, 3/7/17 - "resveratrol, a compound in the skin of red grapes and red wine, and metformin, a drug often prescribed to fight type 2 diabetes, have many of the neuroprotective benefits of a low-calorie diet and exercise ... resveratrol preserves muscle fibers as we age and helps protect connections between neurons called synapses from the negative effects of aging ... the diabetes drug metformin slowed the rate of muscle fiber aging, but it did not significantly affect aging of neuromuscular junctions. However, the drug may possibly protect synapses in different dosage amounts ... Metformin is an FDA-approved drug to treat diabetes, but our study hints it may also serve the purpose of slowing the motor dysfunction that occurs with aging ... In wine, resveratrol is in such small amounts you could not drink enough of it in your life to have the benefits we found in mice given resveratrol" - See Reserveage Nutrition - Resveratrol with Pterostilbene 500mg, Cellular Age-Defying Formula, 60 veg capsules at Amazon.com and metformin at The Antiaging Store.
• Metformin Still Best as First Type 2 Diabetes Treatment - WebMD, 1/2/17 - "Metformin, unless contraindicated, is an effective treatment strategy because it has better effectiveness, is associated with fewer adverse effects, and is cheaper than most other oral medications ... The escalating rates of obesity in the U.S. are increasing the incidence and prevalence of diabetes substantially. Metformin has the added benefit of being associated with weight loss"
• Metformin influences nitrogen and urea metabolism - Science Daily, 9/14/16 - "metformin intake lowers the levels of the harmful LDL cholesterol by activating the AMPK protein complex ... metformin also modulates the body's nitrogen and urea metabolism ... the activation of the AMPK pathway by metformin affects nitrogen and urea metabolism through a further enzyme***, which thus lowers the citrulline levels ... Accordingly, the scientists suspect that the additional intake of citrulline could have a positive effect on the cardiovascular system in patients being treated with metformin" - See BulkSupplements Pure L-Citrulline Powder at Amazon.com.
• Older Drug May Help Type 1 Diabetics' Heart Health - WebMD, 9/6/16 - "An inexpensive medication normally given to people with type 2 diabetes may help preserve heart health in people with the less common form of diabetes -- type 1 ... Metformin is the standard first-line treatment for type 2 diabetes to help bring blood sugar levels down. It also appears to help repair damaged blood cells by increasing the number of blood vessel (vascular) stem cells"
• Metformin-sustained Weight Loss and Reduced Android Fat Tissue at 12 Months in EMPOWIR (Enhance the Metabolic Profile of Women With Insulin Resistance) - WebMD, 8/2/16 - "carbohydrate-modified diet (CMD) and were then randomized to one of three arms for 6 months (phase 1): CMD alone (D), or in combination with metformin (M), or metformin + rosiglitazone (MR), with rerandomization of the D group to one of the active treatment arms ... Mean (±SD) BW decreased significantly at 12 months in the M arm: 85.1 ± 8.5 kg to 79.8 ± 9.0 kg (P = .0003), with 54% of variance in weight over time explained by M treatment. Mean (±SD) percent android fat decreased significantly in the M and D arms: 53.5 ± 4.8% to 49.3 ± 7.6% (P = .010) and 52.9 ± 6.2% to 48.1 ± 8.7% (P = .021)"
• Which Diabetes Drug Is Best? - WebMD, 7/19/16 - "Metformin, in the absence of contraindications or intolerability, should be the first-line agent to treat patients with type 2 diabetes"
• Metformin Linked to Lower Neurodegenerative Disease Risk - Medscape, 6/11/16 - "The mechanism is unclear, but metformin is known to cross the blood-brain barrier ... The adjusted incidence of developing one or more neurodegenerative diseases per 100 person-years was 2.08 for those who never used metformin, 2.47 for those using metformin less than 1 year, 1.61 for less than 2 years, 1.30 for 2 to 4 years, and 0.49 for 4 or more years ... Compared with no metformin, the hazard ratios for 2 to 4 years of metformin therapy for all neurodegenerative diseases combined was 0.623 and for 4 or more years 0.216 ... The findings were also significant for dementia specifically (0.567 at 2–4 years and 0.252 for 4+ years) and for Parkinson's and Alzheimer's diseases only beyond 4 years (0.038 and 0.229, respectively)" - See metformin at The Antiaging Store.
• Metformin Active in Reducing Colorectal Polyp Recurrence - Medscape, 4/22/16 - "they took patients who underwent resection of polyps/adenomas, and they randomly assigned them to receive a placebo or low-dose metformin, 250 mg daily. The treatment lasted for 1 year ... there was a significant reduction in the number of polyps/adenomas in the metformin-treated group: 38% of patients had recurrent adenomas compared with 57% in the placebo group" - See metformin at The Antiaging Store.
• Diabetes drug, metformin, lowers risk of heart disease deaths better than sulfonylureas - Science Daily, 4/20/16 - "A new analysis of 204 studies involving more than 1.4 million people suggests that metformin, the most frequently prescribed stand-alone drug for type 2 diabetes, reduces the relative risk of a patient dying from heart disease by about 30 to 40 percent compared to its closest competitor drug, sulfonylurea ... Among other findings, the new review revealed that DPP-4 inhibitors, a class of anti-diabetic drugs that were very new at the time of the 2011 review, were clearly less effective at lowering blood sugar levels compared to metformin and sulfonylureas"
• Post-menopausal women taking metformin for diabetes may be at lower risk of cancer - Science Daily, 4/7/16 - "women with diabetes had a 45% greater risk of death from invasive cancer overall when compared to women without diabetes. In addition, among women with diabetes, the risk of cancer death differed significantly between metformin users and nonusers. The researchers noted a trend of decreasing risk of cancer death with increasing duration of metformin use ... Compared to women without diabetes, women with diabetes had a 13% higher risk of developing invasive cancer. These women also face increased risk that ranges from 20% to nearly double the chances of being diagnosed with the following cancers: colon, liver, pancreas, endometrial and non-Hodgkin lymphoma. Results also show that metformin use was associated with better survival in diabetes patients diagnosed with ovarian, colorectal and breast cancer" - See metformin at The Antiaging Store.
• Diabetes Drugs Have Positive Effect in MS - Medscape, 3/22/16 - "After a mean follow-up of 26.7 months, patients receiving metformin or pioglitazone had a significant decrease in the number of new or enlarging T2 lesions on brain MRI compared with the control group and compared with findings on MRIs performed 2 years before ... This decrease was evident even after 6 months of treatment. The lowest mean number of new or enlarging T2 lesions occurred after 18 months of treatment (metformin, 0.5; pioglitazone, 0.6) and remained low throughout the study ... There was no significant difference between the two treatments ... Although not designed to detect treatment effects, the study did find that fasting glucose levels, fasting insulin levels, insulin resistance, total cholesterol, low-density lipoprotein cholesterol, triglycerides, and systolic blood pressure all declined significantly in both treatment groups after 12 months"
• How diabetes drug metformin inhibits progression of pancreatic cancer - Science Daily, 1/14/16 - "metformin decreases the inflammation and fibrosis characteristic of the most common form of pancreatic cancer ... Diabetic patients taking metformin -- a commonly used generic medication for type 2 diabetes -- are known to have a reduced risk of developing pancreatic cancer; and among patients who develop the tumor, those taking the drug may have a reduced risk of death"
• New study indicates that metformin has the potential to prevent and treat preeclampsia - Science Daily, 12/22/15 - "the drug metformin decreases the production of the two toxins elevated in preeclampsia and also helps heal injured blood vessels ... Metformin appears to be the aspirin of the 21st century, because the drug has been discovered to have unexpected health benefits not only in diabetes, but also in polycystic ovarian disease and recent work has highlighted its anti-cancer properties"
• Diabetes Drug Improves Gut Bacteria - WebMD, 12/4/15 - "taking metformin had positive effects on the intestinal bacteria of people with type 2 diabetes. Specifically, the drug improved the ability of the bacteria to produce certain types of short-chain fatty acids that reduce blood sugar levels in different ways"
• Using Antidiabetic Therapies to Treat Alzheimer Disease - Medscape, 8/27/15 - "There are other treatments, such as metformin and the new generation of antidiabetic drugs known as incretins, that have been shown in animal models to have a pro-cognitive effect ... Inflammatory molecules have a negative effect on the brain and also contribute to insulin resistance"
• Metformin May Also Lower LDL Cholesterol: Study Suggests How - Medscape, 8/13/15 - "It appears that "metformin intake activates AMP-activated protein kinase (AMPK) and consequently suppresses fatty-acid desaturase (FADS) genes, which leads to reduced levels of lipid metabolites and LDL cholesterol," ... Our study suggests that metformin might indeed have an additional beneficial effect with regard to cardiovascular diseases among the [type 2] diabetes patients"
• Insulin resistance increases risk for Alzheimer's disease, study finds - Science Daily, 7/27/15 - "examined brain scans in 150 late middle-aged adults, who were at risk for Alzheimer's disease, but showed no sign of memory loss. The scans detected if people with higher levels of insulin resistance used less blood sugar in areas of the brain most susceptible to Alzheimer's. When that happens, the brain has less energy to relay information and function ... If you don't have as much fuel, you're not going to be as adept at remembering something or doing something ... this is important with Alzheimer's disease, because over the course of the disease there is a progressive decrease in the amount of blood sugar used in certain brain regions. Those regions end up using less and less"
• Diabetes medication reduces dementia risk: Analysis of health insurance data suggests preventive effect - Science Daily, 6/23/15 - "Treatment with pioglitazone showed a remarkable side benefit. It was able to significantly decrease the risk of dementia ... The longer the treatment, the lower the risk ... Risk reduction was most noticeable when the drug was administered for at least two years ... Metformin -- another frequently prescribed antidiabetic drug -- also lowered the risk of developing dementia. However, the effect was lower than that of pioglitazone" - See metformin at The Antiaging Store.  Pioglitazone is harder to find.  I've been taking both in low dose for years for various anti-aging advantages.
• Impact of Metformin on Clinical Outcomes in Prostate Cancer - Medscape, 6/9/15 - "Metformin may reduce the risk of biochemical recurrence in prostate cancer"
• Should Antidiabetics Be Prescribed in Prediabetes? - Medscape, 6/4/15 - "it's imperative that we talk to the patient about their prediabetes as soon as their fasting blood glucose level exceeds 100 mg/dL ... As for metformin, based on the ADA guidelines, we could prescribe it as soon as lifestyle and dietary measures fail"
• Key to maintaining muscle strength while we age - Science Daily, 6/2/15 - "Previous research by Steinberg's team has shown that this "metabolic switch" is turned on with exercise as well as commonly-used medications including metformin and salicylate (the active ingredient in Aspirin) ... We know we can turn on the AMPK pathway with intense exercise and commonly-used Type 2 diabetes medications"
• Metformin use associated with reduced risk of developing open-angle glaucoma - Science Daily, 5/28/15 - "patients prescribed the highest amount of metformin (greater than 1,110 grams in two years) had a 25 percent reduced risk of OAG risk compared with those who took no metformin. Every one-gram increase in metformin was associated with a 0.16 percent reduction in OAG risk, which means that taking a standard dose of 2 grams of metformin per day for two years would result in a 20.8 percent reduction in risk of OAG ... this study points out the importance of understanding the potential impact of CR (caloric restriction) mimetic drugs on the risk of developing other medical conditions that affect older persons"
• Metformin Underused in Patients With Prediabetes - Medscape, 5/1/15 - "Metformin was prescribed for only 3.7% of patients with prediabetes, even though it can help prevent the onset of type 2 diabetes ... About one in three Americans has prediabetes ... clinicians can consider metformin in those with impaired glucose tolerance, impaired fasting glucose, or an HbA1c of 5.7% to 6.4%" - Note: Plus many use it for anti-aging.
• Metformin, vitamin D3 show impressive promise in preventing colorectal cancer - Science Daily, 3/24/15 - "Not only did the combination of the two improve outcomes in animal studies, but the dual-compound effect was dramatically better than either option alone. Even better, these impressive results required only modest amounts of metformin and Vitamin D3, making concerns about side effects from mega-dosing entirely moot ... Few colon neoplasias developed in the animals receiving moderate doses of metformin-vitamin D combination ... On average, there was also a 40 percent decrease in the development of polyps in all animals receiving both drugs in combination compared to the control groups" - See vitamin D at Amazon.com.
• Metformin Beats Other Type 2 Diabetes Drugs for First Treatment: Study – WebMD - WebMD, 10/28/14 - "of those started on metformin, only about one-quarter needed another drug to control their blood sugar. However, people who were started on type 2 diabetes drugs other than metformin often needed a second drug or insulin to control their blood sugar levels ... around 40 percent of people taking a sulfonylurea, a thiazolidinedione, or a dipeptidyl peptidase 4 inhibitor (DPP-4 inhibitor) added a second drug to their diabetes treatment regimen during the study. Just 25 percent of those on metformin added an additional oral drug during the study period ... 5 percent of those started on metformin later added insulin to their treatment, according to the study. About 9 percent of those who started on a sulfonylurea, 6 percent started on a DPP-4 inhibitor and 6 percent started on thiazolidinediones, also took insulin"
• Metformin and Lower AF Risk Among Patients With T2DM - Medscape, 10/13/14 - "After adjusting for co-morbidities and medications, metformin independently protected the diabetic patients from new-onset AF with a hazard ratio of .81 (95% confidence interval 0.76–0.86, p < 0.0001). Metformin significantly decreased the extent of pacing-induced myolysis and the production of reactive oxygen species" - [Abstract] - See metformin at The Antiaging Store.
• Prediabetes increases the risk of cancer by 15 percent, study of almost 900,000 people shows - Science  Daily, 9/8/14 - "after controlling for BMI, the presence of prediabetes remained associated with an increased risk of cancer of 22% ... In a site-specific cancer analysis, prediabetes was significantly associated with increased risks of cancer of the stomach/colorectum (relative risk, RR 1.55), liver (RR 2.01), pancreas (RR 1.19), breast (RR 1.19) and endometrium (RR 1.60) (all statistically significant), but not associated with cancer of the bronchus/lung, prostate, ovary, kidney or bladder ... several possible mechanisms could explain the results. First, chronic hyperglycaemia and its related conditions, such as chronic oxidative stress and the accumulation of advanced glycated endproducts (that are made in conditions of excessively high blood sugar) may act as carcinogenic factors. Second, increased insulin resistance leads to increased insulin secretion, which can in turn allow cancer cells to grow and divide ... It should be noted that metformin -- one of several first line therapies available to treat type 2 diabetes -- is now considered as having some 'protective' anticancer properties. Notably, metformin mediates an approximately 30% reduction in the lifetime risk of cancer in diabetic patients. However, whether this is true in prediabetic individuals is not yet known"
• Lifestyle, Metformin, Can Delay Diabetes, 15-Year DPP Data Show - Medscape, 6/16/16 - "randomizing overweight or obese people at high risk for type 2 diabetes to intensive lifestyle change or giving them the oral agent metformin can reduce or delay the development of the disease for as long as 15 years, in some cases ... In 2002, the results of the DPP were reported in the New England Journal of Medicine and showed a dramatic 58% reduction in new type 2 diabetes with the intensive lifestyle intervention and a 31% reduction with metformin compared with controls, in both men and women, across a broad spectrum of races, and across age groups, including the elderly ... He listed a myriad of other conditions that occur more frequently in diabetes, such as cirrhosis, cancer, cognitive decline, depression, sleep apnea, gut problems, fractures, and sexual dysfunction, and noted that diabetes is really "accelerated aging.""
• Anti-diabetic drug slows aging and lengthens lifespan, animal study suggests - Science Daily, 6/2/14 - "Metformin causes a slight increase in the number of harmful oxygen molecules. We found that this makes cells stronger and extends their healthy lifespan ... Other studies in humans have shown that metformin suppresses some cancers and heart disease. Metformin could even be an effective drug for counteracting the general effects of aging, say the researchers" - [Abstract]
• Research explains action of drug that may slow aging, related disease - Science Daily, 5/20/14 - "Rapamycin, an antibiotic and immunosuppressant approved for use about 15 years ago, has drawn extensive interest for its apparent ability -- at least in laboratory animal tests -- to emulate the ability of dietary restriction in helping animals to live both longer and healthier ... this medication has some drawbacks, including an increase in insulin resistance that could set the stage for diabetes ... a combination of rapamycin and another drug to offset that increase in insulin resistance might provide the benefits of this medication without the unwanted side effect ... Laboratory mice that have received rapamycin have reduced the age-dependent decline in spontaneous activity, demonstrated more fitness, improved cognition and cardiovascular health, had less cancer and lived substantially longer than mice fed a normal diet ... the drug metformin can address that concern"
• Metformin Linked to Reduced Risk for Glaucoma - Medscape, 5/13/14 - "The risk for open-angle glaucoma was 25% lower in patients with documented cumulative metformin use of more than 1110 g over 2 years (average dose, 2 g/day) than in those with no metformin use ... The association was dose-dependent, with a 0.01% reduced hazard for open-angle glaucoma with every 1 g increase in metformin ... The greatest risk reduction was associated with the highest baseline risk and the highest glycated hemoglobin (HbA1c) levels ... The findings support the concept that metformin and some other drugs are geroprotective because they produce effects that mimic caloric restriction"
• Should Patients Taking Metformin Also Take Vitamin B12? - Medscape, 12/13/13 - "Vitamin B12 deficiency is estimated to be present in up to 30% of patients with diabetes taking metformin.[1] The risk for vitamin B12 deficiency increases with patient age and the dose and duration of metformin use.[5,7] Concomitant conditions such as suboptimal dietary intake, which is common among vegetarians and alcohol abusers, and malabsorption due to atrophic gastritis, pernicious anemia, chronic pancreatitis, and celiac disease may further increase risk for vitamin B12 deficiency.[5] The combination of metformin with proton pump inhibitors has been reported to have an additive effect on risk for vitamin B12 deficiency ... Screening for vitamin B12 deficiency seems reasonable for all adult patients with diabetes, especially those taking metformin" - See vitamin B12 at Amazon.com.
• Some Diabetes Drugs May Affect Cancer Risk in Women - WebMD, 12/6/13 - "Cleveland Clinic researchers analyzed data from more than 25,600 women and men with type 2 diabetes ... The drugs included "insulin sensitizers," which lower blood sugar and insulin levels in the body by increasing the muscle, fat and liver's response to insulin. The other drugs analyzed were "insulin secretagogues," which lower blood sugar by stimulating beta cells in the pancreas to make more insulin ... The use of insulin sensitizers in women was associated with a 21 percent decreased cancer risk compared to insulin secretagogues, the investigators found. Furthermore, the use of a specific insulin sensitizer called thiazolidinedione was associated with a 32 percent decreased cancer risk in women compared to sulphonylurea, an insulin secretagogue ... there were no significant differences between men who used insulin sensitizers or secretagogues"
• Scientists unlock secrets of diabetes drug - Science Daily, 11/3/13 - "The key is that metformin doesn't work to lower blood glucose by directly working on the glucose. It works on reducing harmful fat molecules in the liver, which then allows insulin to work better and lower blood sugar levels ... Fat is likely a key trigger for pre-diabetes, causing blood sugar to start going up because insulin can't work as efficiently to stop sugar coming from the liver"
• Diabetes drug with chemo, radiation may improve outcomes for lung cancer - Science Daily, 10/23/13 - "Treating aggressive lung cancer with the diabetes drug metformin along with radiation and chemotherapy may slow tumor growth and recurrence ... Metformin, the most-widely used drug for type-2 diabetes, has been shown to have anti-cancer effects on a number of cancers, including prostate and colon"
• Common Diabetes Drugs May Carry Risk, Study Suggests - WebMD, 9/26/13 - "Both metformin (brand names include Glucophage and Fortamet) and sulfonylureas (glyburide and glipizide) are commonly prescribed as first-line therapies for patients and have been available since the 1950s ... Patients who took sulfonylureas only were 58 percent more likely to die from any cause than those who took metformin only ... Sulfonylureas work "by increasing insulin release from the beta cells in the pancreas," while metformin "acts by suppressing glucose production by the liver,""
• Association Between Metformin Use and Risk of Prostate Cancer - Medscape, 9/13/13 - "This large study did not find an association between metformin use and risk of prostate cancer among older men with diabetes, regardless of cancer grade or method of diagnosis" - Note:  I usually don't publish studies that don't show anything but people might see the headlines elsewhere and think otherwise on this one with the way it's worded.
• Metformin May Lower Risk of Prostate Cancer Death, Researchers Say - WebMD, 8/5/13 - "metformin is associated with improved survival among diabetic patients with prostate cancer ... whether metformin can prevent prostate cancer progression in people without diabetes remains to be seen ... those who took metformin had a 24 percent reduction in risk from prostate cancer death for every additional six months of use after their cancer diagnosis. The risk reduction of death from other causes was initially the same but declined over time ... No reduction in death risk was seen for patients taking any other diabetes drug ... other diabetes drugs work by increasing the body's insulin production, metformin is an "insulin sensitizer" that works by making the body more sensitive to the insulin already produced ... Some research suggests that high insulin levels can influence cancer growth. Metformin, by not increasing the body's insulin production, may decrease cancer cells' growth, some experts say" - Note:  Metformin is another one that I take in low dose for anti-aging.
• Pill linked to long life in mice - BBC News, 7/31/13 - "Scientists believe the drug, metformin, may mimic the effects of extreme calorie restriction ... Metformin is one of the most widely prescribed treatments for type-2 diabetes, which occurs mainly in people above the age of 40. It is also used to treat metabolic syndrome, a combination of diabetes, high blood pressure and obesity ... The scientists gave one of two different doses of metformin to middle-aged male mice and found that lower doses increased lifespan by about 5%, and also delayed the onset of age-associated diseases" - Note:  I've been taking it in low doses for years to help combat aging.
• Diabetes Drug May Protect the Brain - WebMD, 7/15/13 - "Metformin makes muscle tissue more receptive to insulin, a hormone necessary for sugar (glucose) to get into the body's cells and tissues to provide fuel. It also decreases the amount of glucose made in the liver. Sulfonylureas stimulate the production of insulin. TZDs make muscle and fat tissue more receptive to insulin, and they decrease the amount of glucose made in the liver ... Compared to people taking sulfonylureas, those on metformin had a 20 percent decreased risk of developing dementia, according to the study. There was no difference in dementia risk for those on TZDs or insulin compared to those on sulfonylureas ... one theory stemming from animal research is that metformin may play a role in the development of new brain cells (neurogenesis). It has also been linked to reduced inflammation ... A drug like metformin, [which is] an insulin sensitizer in the body, may also be an insulin sensitizer in the brain" - See metformin at The Antiaging Store.
• CVD Reduced With Metformin, Higher With Rosiglitazone - Medscape, 6/24/13 - "In 29 different studies, metformin was associated with a 10% reduction in the risk of cardiovascular events, with the drug associated with a 10% reduction in the risk of heart failure in seven studies and a 12% reduction in the risk of MI in nine studies. In contrast, rosiglitazone was associated with a 21% increased risk of cardiovascular events in 25 studies, a 27% increased risk of heart failure in 13 studies, and a 17% increased risk of MI in 21 studies"
• How diabetes drug delays aging in worms - Science Daily, 3/28/13 - "Following a calorie-restricted diet has been shown to improve health in later life and extend lifespan in a number of animals, ranging from the simple worm to rhesus monkeys. The type 2 diabetes drug metformin has been found to have similar effects in animals ... Overall, treatment with metformin adds up to 6 days of life for the worm which is equivalent to around a third of its normal lifespan. It seems to work by altering metabolism in the bacteria that live in the worm, which in turn limits the nutrients that are available to the worm host and has a similar effect to restricting the diet ... However, when they added an excess of sugar to the diet, the team found that the life-extending effects of metformin were cancelled out" - See metformin at The Antiaging Store.
• Scientists discover how drug prevents aging and cancer progression - Science Daily, 3/26/13 - "the antidiabetic drug metformin reduces the production of inflammatory cytokines that normally activate the immune system, but if overproduced can lead to pathological inflammation, a condition that both damages tissues in aging and favors tumor growth ... Our studies now point to one mechanism"
• Diabetes drug could hold promise for lung cancer patients - Science Daily, 1/28/13 - "Ever since discovering a decade ago that a gene altered in lung cancer regulated an enzyme used in therapies against diabetes, Reuben Shaw has wondered if drugs originally designed to treat metabolic diseases could also work against cancer ... phenformin, a derivative of the widely-used diabetes drug metformin, decreased the size of lung tumors in mice and increased the animals' survival ... Metformin and phenformin both inhibit mitochondria; however, phenformin is nearly 50 times as potent as metformin ... The Food and Drug Administration took phenformin off the market in 1978 due to a high risk of lactic acid buildup in patients with compromised kidney function, which is not uncommon among diabetics but less of an issue for most cancer patients"
• Diabetes Drug Metformin May Fight Cancer - WebMD, 12/3/12 - "The study is just one of dozens under way worldwide examining the drug -- which costs just pennies a pill -- as a treatment for breast, colon, prostate, pancreatic, and ovarian cancers ... After five years, 67% of women who took metformin had not died from ovarian cancer, compared to 47% of women without diabetes who did not take the drug ... The survival difference in the two groups was striking ... Every way we looked at this, the metformin group always did better ... If metformin really does fight cancer, it may do so by lowering circulating insulin levels in the blood" - [Science Daily]
• Metformin offers cardio benefits over Sulfonylureas in diabetes, study suggests - Science Daily, 11/7/12 - "We demonstrated that for every 1,000 patients who are using metformin for a year there are two fewer heart attacks, strokes or deaths compared with patients who use sulfonylureas. I think this reinforces the recommendation that metformin should be used as the first medication to treat diabetes" - See metformin at The Antiaging Store.
• Metformin May Help Renew Neurons - Medscape, 7/10/12 - "Animal studies showed that metformin activates a key pathway (aPKC-CBP) that promotes neurogenesis and enhanced hippocampus-dependent spatial memory formation in study animals. Results also showed that the drug has similar activity on human neural precursors, increasing the likelihood that it might enhance neurogenesis in the human brain as well ... compared with mice given a control substance, those treated with metformin had about a third more new neurons in the hippocampus, and almost double the number of new neurons produced by stem cells ... in a spatial learning maze test, mice given metformin (200 mg/kg) were significantly better able to learn the location of a submerged platform compared with those given a sterile saline solution"
• Diabetes drug may someday repair Alzheimer's damage - MSNBC, 7/6/12 - "The diabetes medication was intended to target a specific pathway in liver cells. In the new study, researchers found that the drug activated that same pathway in brain cells, prompting new cell growth ... The new cells that are produced could help to repair the effects of neurodegenerative disorders, such as Alzheimer’s disease ... new brain cells grew in both living mice and in human brain cell cultures growing in lab dishes. They are now working to set up clinical trials ... A 2008 study found that patients with both diabetes and Alzheimer’s who began taking metformin experienced improvements in their Alzheimer's symptoms after starting on the drug"
• Metformin may lower cancer risk in people with type 2 diabetes - Science Daily, 6/25/12 - "the odds of getting any type of cancer was 0.62 times less -- an estimated 38 percent relative risk reduction -- with daily continuous use of metformin than for those with no exposure to metformin ... This risk reduction with metformin use extended to certain types of cancers, specifically colon and breast cancer ... Metformin, which is the standard recommended initial treatment of Type 2 diabetes, may protect against cancer because it regulates activity of an enzyme that suppresses cell growth"
• Metformin, Other Antidiabetic Drugs, and Alzheimer's Risk - Medscape, 6/20/12
• Vitamin B12 Deficiency With Metformin Linked to Neuropathy - Medscape, 6/15/12 - "In patients with type 2 diabetes taking metformin, vitamin B12 deficiency is associated with higher levels of peripheral neuropathy ... Chronic metformin use has been previously shown to be associated with vitamin B12 deficiency. Peripheral neuropathy is typically diagnosed as diabetic neuropathy, but this can also be a symptom of vitamin B12 deficiency ... I think we must be careful about older patients and patients who take metformin for a long time. We must measure levels of vitamin B12. We don't change therapies [at our institution], but we treat deficiencies with B12 supplements" - See vitamin B12 at Amazon.com.
• Diabetes drug could treat leading cause of blindness: Metformin blocks uveitis in rats - Science Daily, 5/7/12 - "In laboratory rat and cell-culture experiments, the scientists found that metformin, which is commonly used to control blood sugar levels in type 2 diabetes, also substantially reduced the effects of uveitis, an inflammation of the tissues just below the outer surface of the eyeball. Uveitis causes 10 to 15 percent of all cases of blindness in the United States, and is responsible for an even higher proportion of blindness globally ... Metformin inhibits the process that causes that inflammation"
• Kids With Type 2 Diabetes: Combo Treatment Best? - WebMD, 4/29/12 - "Combined treatment with the diabetes drugs metformin and Avandia proved more effective than metformin alone or metformin plus lifestyle changes for keeping blood sugar at normal levels ... 38% of patients who took metformin and Avandia failed treatment ... 46% of patients in the metformin and lifestyle part of the study failed treatment" - Note:  That was the combo I picked years ago for diabetes prevention even though I don't have diabetes.  See Avandia (rosiglitazone) at OffshoreRx1.com.
• Metformin can substantially reduce the risk of Parkinson's disease in diabetes, study suggests - Science Daily, 4/16/12 - "metformin seems to be working to protect the brain against neurodegeneration which contributes to Parkinsonismin. This means it may also be considered a relevant therapy for the prevention of dementia as well ... A similar benefit would be expected from exercise and diet because that too is a way of establishing healthy energy regulation not only for the whole body, but for tissues and cells in the brain"
• Metformin may lower risk for oral cancer development - Science Daily, 3/31/12 - "administration of metformin reduced the size and number of carcinogen-induced oral tumoral lesions in mice and significantly reduced the development of squamous cell carcinomas by about 70 to 90 percent"
• Metformin may protect against liver cancer - Science Daily, 3/31/12 - "chemically induced liver tumors in mice. The mice taking metformin displayed minimal tumor activity, while the control mice displayed significant tumor growth ... Girnun's team also showed that metformin prevented liver cancer in part by inhibiting lipid synthesis in the liver, a process known to promote cancer"
• Metformin appeared to slow prostate cancer growth - Science Daily, 3/31/12 - "evaluated 22 men with confirmed prostate cancer who had been assigned up to 500 mg of metformin three times a day prior to undergoing prostatectomy ... Patients were assigned metformin for a median duration of 41 days ... metformin significantly reduced fasting glucose, insulin growth factor-1, body mass index and waist-to-hip ratio ... metformin appeared to reduce the growth rate of prostate cancer in a proportion of men"
• Metformin Associated With Lower Cancer Risk - Medscape, 3/26/12 - "During up to 10 years of follow-up, metformin users were less likely to receive cancer diagnoses than sulfonylurea users (hazard ratio, 0.9; 95% confidence interval, 0.88–0.91) after adjustment for age, sex, and several other variables. This 10% reduction was modest in relative terms but highly statistically significant. Metformin-associated lower risks were noted for cancers of the esophagus, stomach, colon, liver, pancreas, lung, breast, and prostate ... If hyperinsulinemia really does promote cancer, metformin theoretically could lower cancer risk in type 2 diabetic patients because it lowers circulating glucose and insulin levels in patients with insulin resistance and hyperinsulinemia"
• Diabetes drug can prevent heart disease, new study suggests - Science Daily, 3/25/12 - "one of the most common diabetes drugs, metformin, also has a protective effect on the heart ... metformin helps increase pumping capacity, improve energy balance, reduce the accumulation of fat, and limit the loss of heart cells through programmed cell death"
• Brain insulin resistance contributes to cognitive decline in Alzheimer's disease - Science Daily, 3/23/12 - "This is the first study to directly demonstrate that insulin resistance occurs in the brains of people with Alzheimer's disease ... Our research clearly shows that the brain's ability to respond to insulin, which is important for normal brain function, is going offline at some point ... We believe that brain insulin resistance may be an important contributor to the cognitive decline associated with Alzheimer's disease ... The risk of developing Alzheimer's disease is increased by 50 percent in people with diabetes ... insulin resistance of the brain occurs in Alzheimer's disease independent of whether someone has diabetes ... The investigators used samples of postmortem brain tissue from non-diabetics who had died with Alzheimer's disease, stimulated the tissue with insulin, and measured how much the insulin activated various proteins in the insulin-signaling pathways ... three insulin-sensitizing medicines are already approved by the FDA for treatment of diabetes. These drugs readily cross the blood-brain barrier and may have therapeutic potential to correct insulin resistance in Alzheimer's disease and MCI" - Note:  I suspected this for a long time.  It doesn't say what those three drugs are but I'm guessing metformin and Actos are two of them.  I don't have diabetes but I take low doses of both.  My doc says I'm crazy.
• Diabetes drug shows promise in reducing risk of cancer, study suggests - Science Daily, 11/23/11 - "People with Type-2 diabetes are known to be at high risk for several diabetes-associated cancers, such as breast, liver and pancreatic cancers ... While metformin has been shown in population studies to reduce the risk of these cancers, there was no evidence of how it worked ... estrogen and the chemicals caused the mammospheres to increase in numbers and size. However, with metformin added, the numbers and size of the mammospheres were dramatically reduced. While each of the chemicals enhanced growth by different means, metformin seemed to be able to inhibit their stimulated growth in all cases"
• Diabetes drug may prevent or delay development of polycystic ovary syndrome, the most common cause of infertility in women - Science Daily, 6/29/11
• Some diabetes drugs are better than others, according to new study - Science Daily, 4/6/11 - "compared to metformin treatment, monotherapy with most ISs, including glimepiride, glibenclamide, glipizide and tolbutamide, was associated with a greater risk of death from any cause, and a greater risk of heart attacks, stroke or death from cardiovascular diseases. This was the case both for patients who had already suffered a heart attack and for patients who had not. Two other ISs, gliclazide and repaglinide, showed no significant difference to metformin in their effectiveness in patients with and without a history of heart attacks ...Patients taking metformin had the best outcomes, supporting prior evidence of metformin benefit and making it the first-line drug recommended for almost all patients with type 2 diabetes. Compared against this beneficial drug, most of the ISs were associated with worse outcomes, but they would almost certainly be similar to, or better, had the comparison been made against placebo treatment, with the added benefit on kidney, eye, and nerve disease of the glucose control they yield" - Note:  Why would they have a study like that and not include the #2 diabetes drug a thiazolidinedione, Actos (pioglitazone).  Makes you question their motives.  See http://www.pharmacytimes.com/media/pdf/PHTM_36.pdf.
• Diabetes treatment may also provide protection against endometrial cancer - Science Daily, 4/5/11 - "Recent research has found that metformin has anti-cancer properties, e.g., in breast cancer ... samples from PCOS women who had completed the 6 month course of metformin the rate of spread of endometrial cancer cells was around 25% lower than in the serum samples from PCOS women who had not started that treatment"
• Newer doesn't mean better when it comes to type 2 diabetes drugs - Science Daily, 3/14/11 - "metformin, an oral drug that was first approved by the U.S. Food and Drug Administration in 1995, not only controlled blood sugar, but was also less likely to cause weight gain or raise cholesterol levels ... even though there are all these newer drugs, metformin works just as well and has fewer side effects ... while two drugs worked better than one in those patients whose blood sugar remained poorly controlled on a single medication, there were also side effects associated with adding a second medication"
• Diabetes drug could work against Alzheimer's, animal study suggests - Science Daily, 11/24/10 - "the diabetes drug metformin counteracts alterations of the cell structure protein Tau in mice nerve cells. These alterations are a main cause of the Alzheimer's disease ... If we can confirm that metformin shows also an effect in humans, it is certainly a good candidate for an effective therapy on Alzheimer's diseases"
• Metformin Might Prevent Colorectal, Lung Cancers - Medscape, 9/3/10 - "The chance observation that diabetes patients taking metformin have a 40% reduced risk for cancer triggered intense research interest in this old off-patent drug ... After about 10% of the mouse lifespan — about 12 weeks — with the highest dose in the drinking water, we found a 33% reduction in tumor multiplicity and a 34% reduction in tumor size in the mice. In mice that did not get metformin, 100% got tobacco carcinogen-induced lung tumors ... metformin might prevent tumors by reducing levels of insulin and IGF-1" - See my Insulin and Aging page.  There are a lot of studies pointing toward insulin being a major cause of aging and caner.
• Well-defined quantity of antioxidants in diet can improve insulin resistance, study finds - Science Daily, 6/21/10 - "For groups C and D, the researchers prescribed a diet enriched in antioxidant, with a calculated intake, 800 to 1,000 milligrams a day, coming from fruits and vegetables, but group D also took metformin ... Despite similar weight loss in all the groups, only the two groups receiving the antioxidant diet (groups C and D) had a significant decrease in insulin resistance ... Group D had the best improvement in insulin resistance on some measures of insulin response to an oral glucose tolerance test ... We think that a total antioxidant level of 800 to 1,000 milligrams a day is safe and probably not close to the maximum tolerable level"
• Metformin-Induced Vitamin B12 Deficiency Presents as Peripheral Neuropathy: Abstract and Introduction - Medscape, 4/22/10
• Metformin may prevent lung cancer in smokers, early research suggests - Science Daily, 4/19/10
• Insulin used to treat diabetes may be linked to increased cancer risk, review suggests - Science Daily, 3/2/10 - "Research suggests that metformin, which is used to treat some patients with diabetes, may provide a protective effect, while insulin and/or certain insulin analogues may promote tumour growth ... Diabetic patients were 30 per cent more likely to develop colorectal cancer ... Women with diabetes had a 20 per cent greater risk of developing breast cancer ... People with diabetes had an 82 per cent higher risk of developing pancreatic cancer" -  Note:  See my Insulin and Aging page.  I think it's like what came first the chicken or the egg.  I don't believe they know whether it's the insulin or the high blood sugar.  This seems to support that it's the high insulin.
• Diabetes Drug Metformin Has Fishy Odor - WebMD, 2/16/10
• Metformin May Help Obese Teens Lose Weight - WebMD, 2/1/10
• Metformin is safe for patients with advanced heart failure and diabetes mellitus, study shows - Science Daily, 1/7/10 - "The study results suggest that, in patients with both advanced heart failure and diabetes, use of metformin is safe, and may be associated with better heart failure survival"
• Click here of a 10/5/09 news clip (I put it on YouTube) that claims that metformin may provide the same anti-aging benefits as calorie restriction (you won't need to look like a POW).  Metformin is another one I take for anti-aging.  In addition to the calorie restriction type benefits, see my Insulin and Aging page.
• Metformin vs. Sulfonylureas for Diabetes - WebMD, 12/4/09 - "Researchers reported that diabetes patients who used sulfonylureas had a higher risk of death from all causes and a higher risk of heart failure than diabetes patients who used the most widely prescribed diabetes drug, metformin ... Compared with metformin, also known as Glucophage, single-drug treatment with first- and second-generation sulfonylureas was associated with up to a 61% increased risk for death. Users of second-generation sulfonylureas had up to a 30% higher risk for congestive heart failure ... Patients treated with Actos or Avandia did not appear to have a greater risk for heart attacks than those treated with metformin"
• Metformin Lowers Serum TSH Levels in Diabetics With Hypothyroidism - Medscape, 10/2/09
• Diabetes Drug Fights Breast Cancer - WebMD, 9/14/09 - "And in mice carrying human breast cancers, metformin made standard chemotherapy vastly more effective. Mice treated with the combination remain cancer-free for four months, unlike mice treated with either drug alone ... A lot of data shows lower cancer risk -- not just breast cancer -- in people taking metformin for diabetes ... This drug at low doses can be considered a very good candidate for cancer prevention before a person has any cancer at all" - Note:  I've been taking metformin for years for anti-aging.  See my Insulin and Aging page.
• Metformin Linked to B12 Deficiency - WebMD, 6/8/09 - "40% of type 2 diabetes patients using metformin had vitamin B12 deficiency or were in the low-normal range for the essential vitamin. And 77% of metformin users with vitamin B12 deficiency also had peripheral neuropathy, a common form of nerve damage associated with type 2 diabetes" - See vitamin B-12 at Amazon.com.
• Common Diabetes Drug May 'Revolutionize' Cancer Therapies: Unexpected T-cell Breakthrough - Science Daily, 6/4/09 - "We used metformin, which is known to operate on fatty-acid metabolism, to enhance this process, and have shown experimentally in mice that metformin increases T-cell memory as well as the ensuing protective immunity of an experimental anti-cancer vaccine"
• 'Cancer hope' from diabetes drug - BBC News, 6/3/09 - "Tests on mice found metformin, used for Type 2 diabetes, helps the body's T-cells work more effectively"
• Old Diabetes Drug Teaches Experts New Tricks - Science Daily, 5/20/09
• Metformin May Have Long-Term Benefits in Patients With Type 2 Diabetes - Medscape, 4/10/09 - "Compared with the placebo group, the metformin group had prevention of weight gain (mean weight gain, −3.07 kg; range, −3.85 to −2.28 kg; P < .001), better glycemic control (mean reduction in glycated hemoglobin level, 0.4%; 95% confidence interval [CI], 0.55 – 0.25; P < .001), and lower insulin requirements (mean reduction, 19.63 U/day; 95% CI, 24.91 – 14.36 U/day; P < .001) ... Add-on metformin improved glycemic control and reduced body weight and insulin requirements"
• Do Diabetes Drugs Affect Heart Health? - WebMD, 10/27/08 - "metformin seemed to be associated with a decrease in heart disease and heart-related deaths ... researchers point to metformin as a drug that is "moderately protective" and Avandia as "possibly harmful." ... Avandia, which works well to reduce blood sugar, was associated with a higher risk of heart attack. However, researchers in that case also acknowledged that their conclusions were limited by a lack of access to original clinical data"
• Metformin May Enhance Weight Loss in Female Adolescents - Medscape, 7/8/08 - "a significant decrease in body mass index was seen in females receiving metformin but not in those taking placebo. Sixty percent of participants who were metformin-adherent and who decreased food portion sizes had a decrease in body mass index of more than 5%" - See metformin at OffshoreRx1.com.
• Metformin Increases Pathologic Complete Response Rates In Breast Cancer Patients With Diabetes - Science Daily, 6/2/08 - "the pathologic complete response rates in the diabetic breast cancer patients taking Metformin was 24 percent, three times higher than the rates in diabetic patients not taking the drug, 8 percent. In the non-diabetic women, the pathologic complete response rate was 16 percent"
• Metformin May Up Alzheimer's Protein if Used Alone - Medscape, 10/15/09 - "I think Chen's study is very important and strengthens the concept of diabetes medication effects on Alzheimer's neuropathology, but at this point I do not think that there is clinical evidence for clinicians to be concerned when treating their diabetic patients with metformin"
• Metformin Alone or With Insulin May Be Safe in Gestational Diabetes - Medscape, 5/7/08
• No Benefits Seen With Metformin for Insulin Resistance in Obese Children: Presented at ECE - Doctor's Guide, 5/7/08
• Thiazolidinediones May Act Against Psoriasis - Medscape, 3/26/08 - "The adjusted odds ratio for a first time diagnosis of psoriasis in current users of five or more prescriptions for thiazolidinediones was 0.33, as compared to no use. The adjusted odds ratio for metformin was 0.77" - See pioglitazone at OffshoreRx1.com.
• Metformin May Delay Onset of Diabetes in At-Risk Subjects - Medscape, 3/24/08 - "Metformin treatment, compared with placebo or no treatment, reduced body mass index by 5.3%, fasting glucose by 4.5%, fasting insulin by 14.4%, and calculated insulin resistance by 22.6% ... Metformin treatment also reduced triglycerides and LDL cholesterol by 5.3% and 5.6%, respectively, and increased HDL cholesterol by 5.0% ... The incidence of new-onset diabetes was reduced by 40% (odds ratio, 0.6), with an absolute risk reduction of 6%, during a mean trial duration of 1.8 years" - I don't have diabetes yet still take 1,000 mg of metformin per day.  I still feel high blood sugar and advanced glycation end products are major causes of aging.  See metformin at OffshoreRx1.com.
• Insulin-Resistant Cardiomyopathy - Medscape, 1/15/08 - "Increasing evidence points to insulin resistance as a primary etiologic factor in the development of nonischemic heart failure (HF) ... Epidemiological evidence suggests more than simply a correlation between insulin resistance and HF, demonstrating that insulin resistance precedes HF rather than occurring as a consequence of it ... Medications that work primarily by improving insulin sensitivity (metformin, thiazolidinediones [TZDs]) might theoretically be the most attractive therapies" - See my web page on Insulin and Aging.
• Metformin, Lifestyle Changes Effective in Antipsychotic-Induced Weight Gain - Medscape, 1/10/08 - "Lifestyle intervention plus metformin had the greatest effect on weight loss, and metformin alone was more effective than lifestyle intervention plus placebo in increasing insulin sensitivity and reversing weight gain in these patients with schizophrenia and significant weight gain from atypical antipsychotic agents"
• Prevention of Type 2 diabetes: fact or fiction? - Expert Opin Pharmacother. 2007 Dec;8(18):3147-58 - "The Diabetes Prevention Program revealed that metformin 850 mg b.i.d. reduced the risk of diabetes by 31%"
• Drug May Help Pregnant Women with Insulin Resistance - Doctor's Guide, 9/6/07 - "metformin, the most commonly prescribed anti-diabetes drug, could potentially improve pregnancy outcomes in women with insulin resistance"
• Diabetes Drug Kills Some Cancer Cells - Science Daily, 8/14/07 - "Four weeks later, the p53-deficient tumors in mice treated with metformin were half the size of the p53 deficient tumors in control mice"
• Older Is Better: Top Ten Comparison Of Diabetes Drugs Give Metformin Top Grade - Science Daily, 7/25/07 - "Metformin was found to lower LDL or bad cholesterol by about 10 milligrams per deciliter of blood, while newer medications studied, such as pioglitazone (Actos) and rosiglitazone (Avandia), or so-called thiazolidinediones, were found to have the opposite effect, increasing levels of the artery-clogging fat by the same amount"
• Old Diabetes Drug Has Advantages - WebMD, 7/16/07
• The Role of Metformin and Pioglitazone in Early Combination Treatment - Medscape, 2/6/07 - "Both metformin and pioglitazone have positive effects on cardiovascular risk factors. Pioglitazone may reduce the progression to type 2 diabetes by effects on both pancreatic beta-cell deterioration and insulin resistance"
• Diabetes Drugs Compared - WebMD, 12/6/06 - "Avandia had the lowest treatment failure rate -- 15% -- compared with 21% for Glucophage and 34% for Micronase"
• Drug 'Avandia' May Prevent Diabetes - WebMD, 9/15/06 - "People at high risk for diabetes who took the drug Avandia reduced their risk of developing the disease by 60% in the three-year trial ... taking the drug metformin (Glucophage), which is already widely used for diabetes prevention, was associated with a 31% reduction in disease risk -- about half that seen in the Avandia study"
• New EASD/ADA Consensus Recommends Metformin at Diagnosis of Type 2 Diabetes - Doctor's Guide, 9/13/06 - "metformin significantly reduced the risk of fatal and non-fatal cardiovascular events in patients with type 2 diabetes(3). The study showed a 36% reduction in all-cause mortality, a 42% reduction in diabetes-related mortality and a 32% reduction in diabetes-related endpoints"
• FDA Approves Avandamet (Rosiglitazone Maleate and Metformin HCl) as Initial Therapy in the Treatment of Type 2 Diabetes - Doctor's Guide, 7/11/06
• Metformin Induces Long-Term Weight Loss in Teens - Doctor's Guide, 6/28/06 - "Metformin can induce long-term weight loss in obese, non-diabetic adolescents, and could possibly be useful in a regimen to help achieve weight loss in adolescents, who may have developed type 2 diabetes type due to overweight"
• Depression Drugs May Up Diabetes Risk - WebMD, 6/12/06 - "taking antidepressants was associated with a two- to threefold increase in risk ... The increase was not seen, however, in people at high risk for diabetes who were taking both antidepressants and the blood-sugar-regulating drug glucophage (metformin)"
• Can Metformin Help Teenagers With PCO? - Medscape, 4/19/06
• Metformin and Lifestyle Intervention May Help Prevent Metabolic Syndrome - Medscape, 4/18/06 - "Participants were randomly assigned to standard treatment with placebo pill; metformin, 850 mg, twice daily; or intensive lifestyle management with placebo pill and followed up for a mean of 3.2 years ... Intensive lifestyle consisted of reduction of at least 7% of body weight, low-calorie and low-fat diet, and moderate physical activity at least 150 minutes weekly ... In those with prevalent MS at baseline ... At 3 years 18% of the placebo, 23% of the metformin, and 38% of the lifestyle intervention group no longer had the MS, with lifestyle intervention only showing a significant effect vs placebo"
• Newer Diabetic Meds Cost More, But Users Have Fewer Hospital Visits - Science Daily, 3/24/06 - "Taking a TZD as instructed was the strongest predictor of a reduced risk of hospitalization and decreased healthcare costs in this group of patients ... Overall, the participants who took a TZD spent an average of $76 to $150 less per month on total healthcare costs" - See OffshoreRx1.com.
• Metformin-Associated Lactic Acidosis Can Be Aggravated by Antihypertensive Drugs in Diabetics - Doctor's Guide, 11/14/05 - "Concurrent use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and metformin could aggravate the risk of metformin-associated lactic acidosis"
• Metformin Increases Ovulation in Women with Polycystic Ovary Syndrome Better than Clomiphene Citrate - Doctor's Guide, 10/21/05
• Metformin May Be Safer Than Sulfonylureas in Patients With Diabetes and Heart Failure - Medscape, 9/30/05
• ACTOplus Met Approved by the FDA for Type 2 Diabetes - Doctor's Guide, 8/30/05 - "ACTOplus met combines ACTOS (pioglitazone HCl) and metformin, two widely used diabetes medications, in a single tablet"
• Review: Metformin a Top Diabetes Drug - WebMD, 7/19/05 - "Though many of the newer drugs may promote weight gain, metformin has been associated with modest weight losses in people with type 2 diabetes"
• Metformin Works Well as Monotherapy in Type 2 Diabetes Especially in Overweight or Obese Patients - Doctor's Guide, 7/15/05
• Metformin May Be Best First-Line Therapy for Anovulatory Women With Polycystic Ovary Syndrome - Medscape, 4/29/05
• Metformin and Lifestyle Intervention May Help Prevent Metabolic Syndrome - Medscape, 4/18/05 - "metformin therapy (850 mg twice daily) ... Compared with placebo, the lifestyle group had 41% lower incidence of the MS (P < .001), and the metformin group had 17% lower incidence"
• Vitamin B12 Status of Patients Treated With Metformin - Medscape, 2/17/05 - "Patients exposed to long-term metformin therapy had 26.7% lower cobalamin, 21.6% lower holotranscobalamin and 9.7% higher HCy serum concentrations than control subjects. Such changes indicate a potential risk for development of vitamin B12 deficiency"
• Research Highlights Hormonal Control of Cardiovascular Functions - Doctor's Guide, 8/17/04 - "The Patients who received metformin experienced an improvement in several endothelial function markers, including weight, fasting plasma glucose, soluble intercellular adhesion molecule and soluble vascular cell adhesion molecule"
• Metformin Shows Promise for Diabetes Prevention, but Further Studies Needed - Doctor's Guide, 6/24/04 - "After 1 year of treatment, patients receiving metformin experienced a significantly lower increase in fasting blood glucose levels compared with the placebo group (3.6 mg/dL vs. 7.2 mg/dL, P < .05)"
• Metformin Can Prevent Girls with Insulin Resistance from Developing Polycystic Ovary Syndrome - Doctor's Guide, 6/21/04 - "Early use of metformin in girls with insulin resistance can decrease the progression to polycystic ovary syndrome (PCOS), a common female endocrine disorder"
• Metformin, Diet/Exercise Comparable at Cutting Diabetes Risk in Women With GDM - Medscape, 6/7/04 - "in women who reported a history of GDM, either metformin or lifestyle changes reduced the relative risk of later type 2 DM by about 54%. In contrast, the relative risk reduction associated with metformin was 14% in women with no history of GDM compared with 51% for lifestyle changes"
• What You Don’t Know About Blood Sugar - Life Extension Magazine, 1/04 - "it now appears that optimal fasting blood glucose levels should probably be under 86 mg/dL ... Chromium supplements have been shown to reduce blood glucose significantly.70-74 The dose used in human studies ranges from 200 to 1000 mcg of elemental chromium a day, with best results occurring when 400 mcg or more of chromium is taken daily ... Nondiabetics using metformin may start off at 500 mg a day and gradually build up to 1000-1500 mg a day. The objective is not to take so much metformin as to induce a hypoglycemic state" - See iHerb chromium products.
• Metformin Treatment Leads to Increased Homocysteine, Decreased Vitamin B12 and Folate in Type 2 Diabetes Patients - Doctor's Guide, 10/20/03 - "Homocysteine requires folate and vitamin B12 to be properly metabolised, and serum vitamin B12 levels are known to decrease during metformin treatment ... compared with placebo, metformin was associated with an increase in serum homocysteine levels (4% [0.2 to 8 µmol L-1]; P=0.039), and decreases in vitamin B12 (-14% [-4.2 to -24 pmol L-1]; P<0.0001) and folate (-7%"
• Uses of Metformin May Extend Beyond Patients with Type 2 Diabetes - Doctor's Guide, 9/4/03 - "In type 2 diabetics, metformin appears to decrease plasma fasting glucose and HbA1c levels without causing weight gain. Metformin may also have a positive influence on a variety of cardiovascular risk factors and may be useful in preventing diabetes in overweight individuals with mild hyperglycaemia ... while further study is necessary before more widespread use is encouraged, the role of metformin may be expanded for glucose control in children and teenagers with type 2 diabetes, in non-diabetic women with PCOS, and to prevent progression to diabetes"
• FDA Approves New Avandamet (Rosiglitazone Maleate/Metformin) Dosage Strengths For Treatment Of Type 2 Diabetes - Doctor's Guide, 8/27/03
• Lifestyle Modification, Metformin Effective Prevention for Type 2 Diabetes - Doctor's Guide, 7/31/03 - "1,073 patients were prescribed 850 mg metformin twice daily, 1,082 had placebo twice daily, and 1,079 were prescribed an intensive program of lifestyle modification ... Incidence of diabetes was 58% lower ... in the lifestyle intervention group and 31% lower ... in the metformin group than in the placebo group"
• BioMarker Pharmaceuticals Develops Anti-Aging Therapy - LE Magazine cover story, 6/03 - "The BioMarker scientists found that all the glucoregulatory agents reproduced some of the gene expression effects of CR [calorie restriction], but that metformin was the undisputed star of the group, being twice as effective as the others in reproducing the effects of CR"
• Benfluorex Improves Glycaemic Control In Type 2 Diabetes - Doctor's Guide, 4/29/03 - "Although benfluorex may be less potent than metformin, it lowers haemoglobin A1C (HbA1C) and fasting plasma glucose levels and is well tolerated"
• Combination Therapy Improves Management of Obese Diabetics - Doctor's Guide, 4/15/03 - "Adding rosiglitazone, an insulin-sensitising thiazolidinedione drug, to metformin, a biguanide agent, greatly enhances the management of obese type 2 diabetic patients who are inadequately controlled by metformin alone"
• Diabetes Prevention Efforts Achieving Good Results - Doctor's Guide, 2/17/03 - "Strategies that may prevent progression to diabetes include weight reduction, exercise, insulin secretagogues, metformin, glucosidase inhibitors and thiazolidinedione ... Diabetes risk was reduced by 31% among patients who were treated with metformin (which tends to restrain weight gain) and by 58% for patients who improved their lifestyle ... Losing even 5 to 7 kg [11 to 15.4 pounds] "has an enormous benefit" that was also apparent in cholesterol and other cardiovascular risk factor reductions"
• Will New Drugs Head Off Diabetes? - WebMD, 5/10/02 - ""We think of IGT [impaired glucose tolerance] and diabetes as parts of what we call the metabolic syndrome. This is something that affects one in four Americans -- and up to half of the U.S. population by age 60. What we have to target is high blood sugar, whether it is IGT or type 2 diabetes." ... One diabetes drug, Glucophage, has already been shown to help prevent type 2 diabetes in people with IGT. But that same study, published in the February 2002 issue of The New England Journal of Medicine, showed that exercise was even better than Glucophage at preventing diabetes"
• The Skinny on Fat Drugs - WebMD, 2/20/02 - "This diabetes drug improves sensitivity to insulin. It seems to prevent weight gain in adults. Studies are under way in overweight people who do not have diabetes. Side effects of Glucophage include nausea, flatulence, bloating, and diarrhea at the beginning of treatment. It can also cause a serious problem -- lactic acidosis -- in some patients with underlying disease"
• How to Stop Diabetes In Its Tracks - WebMD, 2/6/02 - "the study found that the diet/exercise program cut diabetes risk by 58%. Glucophage was significantly less effective, but still decreased risk by 31% ... The diet was centered around lowering fat intake to less than 25% of overall calories ... the 30-minute daily exercise regime "should be easily achievable" by most nondiabetic overweight Americans with high blood sugar levels"
• Metformin Appears Suitable For Children With Type 2 Diabetes - Doctor's Guide, 1/18/02
• Diabetes Drug [Glucophage/metformin] May Fight Obesity - WebMD, 12/26/01 - "Pediatricians at the University of Tennessee School of Medicine put 24 obese adolescents on a low-calorie diet: 1,500 calories a day for the girls and 1,800 calories a day for the boys. They also gave half the teens Glucophage and half a placebo ... After eight weeks, dieting teens who took the placebo lost 3.8 % of their body weight. But those taking Glucophage lost 6.5 % of their body weight -- nearly twice as much"
• The Multiple Benefits of Metformin - Life Extension Magazine, 9/01 - "An ideal anti-diabetic drug would enhance cellular insulin sensitivity, inhibit excess intestinal absorption of sugar, reduce excess liver production of glucose, promote weight loss and reduce cardiovascular risk factors. Metformin (Glucophage) is the one drug that does all of this and more"
• How to Avoid Diabetes -- Landmark Results Unveiled - WebMD, 8/8/01 - "Either a low-fat diet combined with moderate exercise or the drug metformin -- brand name Glucophage -- dramatically reduced type 2 diabetes risk among overweight people with elevated blood sugar"

Abstracts:

• Metformin and Cancer: Solutions to a Real-World Evidence Failure - Diabetes Care 2023 May 1 - "The quest to repurpose metformin, an antidiabetes drug, as an agent for cancer prevention and treatment, which began in 2005 with an observational study that reported a reduction in cancer incidence among metformin users, generated extensive experimental, observational, and clinical research. Experimental studies revealed that metformin has anticancer effects via various pathways, potentially inhibiting cancer cell proliferation. Concurrently, multiple nonrandomized observational studies reported remarkable reductions in cancer incidence and outcomes with metformin use. However, these studies were shown, in 2012, to be affected by time-related biases, such as immortal time bias, which tend to greatly exaggerate the benefit of a drug. The observational studies that avoided these biases did not find an association. Subsequently, the randomized trials of metformin for the treatment of type 2 diabetes and as adjuvant therapy for the treatment of various cancers, advanced or metastatic, did not find reductions in cancer incidence or outcomes. Most recently, the largest phase 3 randomized trial of metformin as adjuvant therapy for breast cancer, which enrolled 3,649 women with a 5-year follow-up, found no benefit for disease-free survival or overall survival with metformin. This major failure of observational real-world evidence studies in correctly assessing the effects of metformin on cancer incidence and outcomes was caused by preventable biases which, surprisingly, are still prominent in 2022. Rigorous approaches for observational studies that emulate randomized trials, such as the incident and prevalent new-user designs along with propensity scores, avoid these biases and can provide more accurate real-world evidence for the repurposing of drugs such as metformin"
• Metformin inhibits neutrophil extracellular traps-promoted pancreatic carcinogenesis in obese mice - Cancer Lett 2023 Apr 6 - "Metformin and DNase I significantly reversed the pro-tumorigenic effects of obesity and NETs in vivo and in vitro" - See metformin at ReliableRX.
• Association between antidiabetic drugs and the incidence of atrial fibrillation in patients with type 2 diabetes: a nationwide cohort study in South Korea - Diabetes Res Clin Pract 2023 Mar 16 - "The combination therapy of MET and TZD is the most effective antidiabetic drug for preventing AF in patients with type 2 diabetes." - See metformin at ReliableRX.
• Metformin and simvastatin exert additive antitumour effects in glioblastoma via senescence-state: clinical and translational evidence - EBioMedicine 2023 Mar 10 - "Glioblastoma is one of the most devastating and incurable cancers due to its aggressive behaviour and lack of available therapies, being its overall-survival from diagnosis ∼14-months. Thus, identification of new therapeutic tools is urgently needed. Interestingly, metabolism-related drugs (e.g., metformin/statins) are emerging as efficient antitumour agents for several cancers ... Altogether, metformin and simvastatin reduce aggressiveness features in glioblastomas, being this effect significantly more effective (in vitro/in vivo) when both drugs are combined, offering a clinically relevant opportunity that should be tested for their use in humans" - See metformin at ReliableRX and simvastatin at ReliableRXPharmacy.
• Τhe Endless Beauty of Metformin: Does It Also Protect from Skin Aging? A Narrative Review - Adv Ther 2023 Jan 30 - "Metformin has shown multiple effects beyond its widely known antidiabetic effect. Impressively, it has already been proposed as an anti-aging factor. However, the potentially protective role of metformin in skin aging, the most common manifestation of aging, is not well examined. Existing evidence based on experimental studies suggests a potential anti-aging effect on skin. Proposed molecular skin anti-aging mechanisms of metformin include mainly reduction of nuclear factor kappa B (NF-κB) (p65) activity. Moreover, metformin appears to inhibit ultraviolet B (UVB)-induced secretion of pro-inflammatory cytokines"
• Metformin in SARS-CoV-2 infection: A hidden path - from altered inflammation to reduced mortality. A review from the literature - J Diabetes Complications 2023 Jan 2 - "Metformin remains on the first line of the management of hyperglycemia in type 2 diabetes. Through its anti-inflammatory and immunomodulatory mechanisms, metformin appears as an opportunity to control the dysregulated cytokine storm secondary to SARS-CoV-2 infection. Recent studies point towards a potential protective role of metformin in the course of COVID-19, showing that current or previous treatment with metformin associates with better outcomes"
• Can Metformin Reduce Need for Total Joint Replacement in Diabetes? - Medscape, 12/20/22 - "Compared with nonusers, metformin users had had a 30% lower risk of total knee or hip replacement (adjusted hazard ratio [HR], 0.70). The incidence of total knee replacement among metformin nonusers and users was 4.15 per 10,000 person-months and 2.96 per 10,000 person-months, respectively. The incidence of total hip replacement was 0.83 per 10,000 person-months in nonusers and 0.44 per 10,000 person-months in users ... By joint type, the adjusted HR was 0.71 for total knee replacement and 0.61 for total hip replacement among metformin users ... The effect was observed at daily doses of less than 1 g, as well as daily doses of 1 g or more. "This suggests that metformin at a lower dosage could have effects on osteoarthritis,"" - See metformin at ReliableRX.
• Metformin is Associated with Reduced COVID-19 Severity in Patients with Prediabetes - Diabetes Res Clin Pract 2022 Nov 15 - "Metformin use is associated with less severe COVID-19 in patients with prediabetes or PCOS"
• The potential benefit of metformin to reduce delirium risk and mortality: a retrospective cohort study - Aging (Albany NY) 2022 Nov 18 - "Metformin has been reported to improve age-related disorders, including dementia, and to lower mortality ... Prevalence of delirium was 36.0% in the DM-without-metformin group, and 29.2% in the DM-with-metformin group. A history of metformin use reduced the risk of delirium in patients with DM (OR, 0.50 [95% CI, 0.32 to 0.79]) after controlling for confounding factors. The 3-year mortality in the DM-without-metformin group (survival rate, 0.595 [95% CI, 0.512 to 0.669]) was higher than in the DM-with-metformin group (survival rate, 0.695 [95% CI, 0.604 to 0.770]) (p=0.035). A history of metformin use decreased the risk of 3-year mortality after adjustment for confounding factors (HR, 0.69 [95% CI, 0.48 to 0.98]) ... Metformin use may lower the risk of delirium and mortality in DM patients"
• Anti-diabetic drug metformin suppresses tumorigenesis through inhibition of mevalonate pathway enzyme HMGCS1 - J Biol Chem 2022 Nov 7 - "Metformin, an antidiabetic drug, shows some potent anti-tumor effects. However, the molecular mechanism of metformin in tumor suppression has not been clarified. Here we provided evidence using in vitro and in vivo data that metformin inhibited mevalonate pathway by downregulation of HMGCS1, a key enzyme in this pathway. Our results further demonstrated that metformin downregulated HMGCS1 expression through inhibition of transcription factor NRF2. Additionally, we determined that HMGCS1 was highly expressed in human liver and lung cancer tissues and associated with lower survival rates. In summary, our study indicated that metformin suppresses tumorigenesis through inhibition of the NRF2/HMGCS1 axis, which might be a potential target in cancer prevention and treatment."
• Metformin mitigates cholesterol accumulation via the AMPK/SIRT1 pathway to protect osteoarthritis chondrocytes - Biochem Biophys Res Commun 2022 Sep 29 - "metformin activated AMPK and SIRT1, mediated by the activation of SREBP-2 and HMGCR in OA chondrocytes. Inhibiting AMPK/SIRT1 activity by its specific inhibitor could suppress IL-1β-induced expression of LXRα, ABCA1 and ApoA1 and cholesterol efflux. Thus, metformin inhibits cholesterol synthesis and promotes cholesterol efflux by activating the AMPK/SIRT1 pathway in OA chondrocytes. This study improves our understanding of the effect of metformin on cholesterol accumulation in OA chondrocytes"
• The role of metformin as a treatment for neuropsychiatric illness - Eur Neuropsychopharmacol 2022 Sep 29 - "Metformin is a widely used hypoglycaemic agent that is now being studied for use beyond diabetes management. Evidence is emerging that metformin has multiple effects on diverse neurobiological pathways and consequently may be repurposed for treating mental illness. Metformin may have beneficial neuroimmunological, neuroplastic, neuro-oxidative and neuro-nitrosative effects across a range of psychiatric and neurodegenerative illnesses. Mechanisms include glucose lowering effects and effects on AMP-activated protein kinase (AMPK) signalling, however the best evidence for clinical benefit is through the glucose lowering effects, with other mechanisms less supported by the current evidence base"
• Metformin, Testosterone Replacement Linked to Reduced Cancer Risk - Medscape, 8/26/22 - "metformin and testosterone replacement therapy were independently and jointly associated with a reduced incidence of prostate cancer, with the greatest reduction with the combination of the two (joint odds ratio [OR],  0.44) ... The two drugs were also inversely associated with a high grade at prostate cancer diagnosis (joint OR, 0.36) and advanced cancer stage (joint OR, 0.47), after multivariate adjustment for factors including age, race/ethnicity, hypogonadism, hypertension, diabetes, insulin use, muscular wasting, and other factors ... Metformin and testosterone replacement therapy were also independently and in combination inversely associated with the incidence of colorectal cancers (joint OR, 0.47); however, the associations with higher grade and advanced stage were not consistent, the authors note" - Note: Good luck with that. Testosterone prescriptions are another one that's like getting a prescription for cocaine. Doctors seem locked in a previous era.
• Rapamycin/metformin co-treatment normalizes insulin sensitivity and reduces complications of metabolic syndrome in type 2 diabetic mice - Aging Cell 2022 Aug 19 - "Rapamycin treatment has positive and negative effects on progression of type 2 diabetes (T2D) in a recombinant inbred polygenic mouse model, male NONcNZO10/LtJ (NcZ10). Here, we show that combination treatment with metformin ameliorates negative effects of rapamycin while maintaining its benefits. From 12 to 30 weeks of age, NcZ10 males were fed a control diet or diets supplemented with rapamycin, metformin, or a combination of both. Rapamycin alone reduced weight gain, adiposity, HOMA-IR, and inflammation, and prevented hyperinsulinemia and pre-steatotic hepatic lipidosis, but exacerbated hyperglycemia, hypertriglyceridemia, and pancreatic islet degranulation. Metformin alone reduced hyperinsulinemia and circulating c-reactive protein, but exacerbated nephropathy. Combination treatment retained the benefits of both while preventing many of the deleterious effects. Importantly, the combination treatment reversed effects of rapamycin on markers of hepatic insulin resistance and normalized systemic insulin sensitivity in this inherently insulin-resistant model. In adipose tissue, rapamycin attenuated the expression of genes associated with adipose tissue expansion (Mest, Gpam), inflammation (Itgam, Itgax, Hmox1, Lbp), and cell senescence (Serpine1). In liver, the addition of metformin counteracted rapamycin-induced alterations of G6pc, Ppara, and Ldlr expressions that promote hyperglycemia and hypertriglyceridemia. Both rapamycin and metformin treatment reduced hepatic Fasn expression, potentially preventing lipidosis. These results delineate a state of "insulin signaling restriction" that withdraws endocrine support for further adipogenesis, progression of the metabolic syndrome, and the development of its comorbidities. Our results are relevant for the treatment of T2D, the optimization of current rapamycin-based treatments for posttransplant rejection and various cancers, and for the development of treatments for healthy aging" - See metformin at ReliableRX and Siromus at ReliableRXPharmacy.
• Metformin, testosterone, or both in men with obesity and low testosterone: A double-blind, parallel-group, randomized controlled trial - Metabolism 2022 Aug 16 - "Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index ... the HOMA-IR index decreased significantly in all active groups compared to placebo (metformin - 2.4, 95 % CI -4.1 to - 0.8, p = 0.004; testosterone - 2.7, 95 % CI -4.3 to - 1.1, p = 0.001; combination - 3.4, 95 % CI -5.0 to - 1.8, p < 0.001). Combination therapy was not superior to testosterone alone in decreasing insulin resistance (-0.7, 95 % CI -2.3 to +0.9, p = 0.383). Only the combination of metformin plus testosterone significantly increased total and free testosterone concentrations, compared to placebo. No significant changes in body composition (except for a higher decrease in fat mass in the metformin and combination group), metabolic variables, erectile function, or HRQoL were found with any treatment"
• Metformin and testosterone replacement therapy inversely associated with hormone-associated cancers (prostate, colorectal and male breast cancers) among older White and Black men - Clin Endocrinol (Oxf) 2022 Jul 28 - "The independent and joint association of metformin and testosterone replacement therapy (TTh) with the incidence of prostate, colorectal, and male breast cancers remain poorly understood, including the investigation of the risk of these cancers combined (HRCs, hormone-associated cancers) among men of different racial and ethnic background ... We found independent and joint associations of metformin and TTh with incident prostate (ORjoint = 0.44, 95% CI: 0.36 - 0.54) and colorectal cancers (ORjoint = 0.47, 95% CI: 0.34 - 0.64), but not with male breast cancer. There were also inversed joint associations of metformin and TTh with HRCs (ORjoint = 0.45, 95% CI: 0.38 - 0.54)"
• Metformin mitigates stress-induced premature senescence by upregulating AMPKα at Ser485 phosphorylation induced SIRT3 expression and inactivating mitochondrial oxidants - Mech Ageing Dev 2022 Jul 18 - "The senescence of vascular smooth muscle cells (VSMCs) is an important cause of cardiovascular disease such as atherosclerosis and hypertension. These senescence may be triggered by many factors, such as oxidative stress, inflammation, DNA damage, and senescence-associated secretory phenotypes (SASPs). Mitochondrial oxidative stress induces cellular senescence, but the mechanisms by which mitochondrial reactive oxygen species (mtROS) regulates cellular senescence are still largely unknown ... This study provides mechanistic evidence that metformin acts as an anti-aging agent and alleviates VSMC senescence by upregulating mitochondrial antioxidant induced p-AMPK (Ser485)-dependent SIRT3 expression, which suggests metformin has therapeutic potential for the treatment of age-associated vascular disease" - See metformin at ReliableRX.
• Metformin Shows Potential to Prevent Macular Degeneration - Medscape, 7/18/22 - "patients who were prescribed the drug over a period of 2 years were about 5% less likely to have AMD ... But the drug has previously shown protective effects against other age-related diseases such as dementia, cancer, and stroke. And it works through pathways that play a role in the development of AMD ... Those patients prescribed low to moderate doses of metformin had the least risk. Those prescribed 1-270 grams over 2 years had an OR of 0.91 (95% CI, 0.88 - 0.94). And those prescribed 271-600 grams over 2 two years had an OR of 0.90 (95% CI, 0.87 - 0.93). But patients prescribed doses over 1080 grams over 2 years did not have reduced odds of developing AMD ... On the other hand, people prescribed the diabetes drugs exenatide, sitagliptin, or pramlintide instead of metformin were at higher risk of developing AMD (OR, 1.08"
• Human age reversal: Fact or fiction? - Aging Cell 2022 Jul 2 - "Although chronological age correlates with various age-related diseases and conditions, it does not adequately reflect an individual's functional capacity, well-being, or mortality risk. In contrast, biological age provides information about overall health and indicates how rapidly or slowly a person is aging. Estimates of biological age are thought to be provided by aging clocks, which are computational models (e.g., elastic net) that use a set of inputs (e.g., DNA methylation sites) to make a prediction. In the past decade, aging clock studies have shown that several age-related diseases, social variables, and mental health conditions associate with an increase in predicted biological age relative to chronological age. This phenomenon of age acceleration is linked to a higher risk of premature mortality. More recent research has demonstrated that predicted biological age is sensitive to specific interventions. Human trials have reported that caloric restriction, a plant-based diet, lifestyle changes involving exercise, a drug regime including metformin, and vitamin D3 supplementation are all capable of slowing down or reversing an aging clock. Non-interventional studies have connected high-quality sleep, physical activity, a healthy diet, and other factors to age deceleration. Specific molecules have been associated with the reduction or reversal of predicted biological age, such as the antihypertensive drug doxazosin or the metabolite alpha-ketoglutarate. Although rigorous clinical trials are needed to validate these initial findings, existing data suggest that aging clocks are malleable in humans" - See metformin at ReliableRX, vitamin D at Amazon.com and alpha ketoglutarate at Amazon.com.
• Metformin Use and Mortality in Women with Ovarian Cancer: An Updated Meta-Analysis - Int J Clin Pract 2022 Feb 28 - "Nine studies including 10030 women with OC were included. Overall, metformin use was independently associated with reduced overall mortality (hazard ratio (HR): 0.72" - See metformin at ReliableRX.
• Metformin Promotes Mechanical Stretch-Induced Skin Regeneration by Improving the Proliferative Activity of Skin-Derived Stem Cells - Front Med (Lausanne) 2022 May 24 - "Skin expansion by mechanical stretch is an essential and widely used treatment for tissue defects in plastic and reconstructive surgery; however, the regenerative capacity of mechanically stretched skin limits clinical treatment results. Here, we propose a strategy to enhance the regenerative ability of mechanically stretched skin by topical application of metformin ... Compared with the control group, metformin treatment was beneficial to mechanical stretch-induced skin regeneration by increasing the thicknesses of epidermis (57.27 ± 10.24 vs. 31.07 ± 9.06 μm, p < 0.01) and dermis (620.2 ± 86.17 vs. 402.1 ± 22.46 μm, p < 0.01), number of blood vessels (38.30 ± 6.90 vs. 17.00 ± 3.10, p < 0.01), dermal collagen volume fraction (60.48 ± 4.47% vs. 41.28 ± 4.14%, p < 0.01), and number of PCNA+, Aurora B+, and pH3+ cells. Additionally, we observed significant elevations in the number of proliferating hair follicle bulge stem cells [cytokeratin (CK)15+/proliferating cell nuclear antigen (PCNA)+] (193.40 ± 35.31 vs. 98.25 ± 23.47, p < 0.01) and epidermal stem cells (CK14+/PCNA+) (83.00 ± 2.38 vs. 36.38 ± 8.96, p < 0.01) in the metformin-treated group, and western blot results confirmed significant increases in CK14 and CK15 expression following metformin treatment"
• Metformin: Is it a drug for all reasons and diseases? - Metabolism 2022 May 28 - "We conclude that the primary clinical benefits of metformin result from its insulin-sensitizing and antihyperglycaemic effects that secondarily contribute to a reduced risk of a number of diseases and thereby enhancing healthspan. However, benefits like improving vascular endothelial function that are independent of effects on glucose homeostasis add to metformin's therapeutic actions"
• Metformin Treatment Among men With Diabetes and the Risk of Prostate Cancer - Am J Epidemiol. 2022 - "With 666,553 person-years of follow-up, 1,592 men were diagnosed with prostate cancer. Metformin exposure in the previous year was positively associated with prostate cancer risk (per defined daily dose; without adjustment for glucose control, hazard ratio (HR) = 1.53 (95% confidence interval (CI): 1.19, 1.96); with adjustment, HR = 1.42 (95% CI: 1.04, 1.94)). However, exposure during the previous 2–7 years was negatively associated with risk (without adjustment for glucose control, HR = 0.58 (95% CI: 0.37, 0.93); with adjustment, HR = 0.60 (95% CI: 0.33, 1.09)). These positive and negative associations with previous-year and earlier metformin exposure, respectively, need to be confirmed and better understood"
• Metformin induced vitamin B12 deficiency can cause or worsen distal symmetrical, autonomic and cardiac neuropathy in the patient with diabetes - Diabetes Obes Metab 2022 May 2 - "Metformin blocks the absorption of vitamin B12 through a mechanism that has not been established but could be due to interference with the calcium-dependent binding of the intrinsic factor- vitamin B12 complex to the cubam receptor in the terminal ileum. The subsequent deficiency of vitamin B12 may cause or accelerate distal symmetrical and autonomic neuropathy in the diabetic patient. Several observational studies and meta-analyses have reported a significant association between metformin utilization and vitamin B12 deficiency. Prospective studies have shown that not only do metformin utilizers have lower vitamin B12 levels but they also have higher frequencies of distal symmetrical polyneuropathy and autonomic neuropathy (including cardiac denervation which is associated with increased incidences of cardiac arrythmias, cardiac events and mortality) ... If serum vitamin B12 levels are borderline, measuring methylmalonic acid (MMA) and homocysteine levels can detect vitamin B12 deficiency at its earliest stage. Therapies include prophylactic calcium and vitamin B12 supplements, metformin withdrawal, replenishing vitamin B12 stores with intramuscular or oral vitamin B12 therapy and regular monitoring of vitamin B12 levels and vitamin B12 supplements if metformin continues to be utilized. With adequate vitamin B12 replacement, while symptoms of neuropathy may or may not improve, objective findings of neuropathy stabilize but do not improve" - See vitamin B12 at Amazon.com.
• Metformin-mediated mitochondrial protection post-cardiac arrest improves EEG activity and confers neuroprotection and survival benefit - FASEB J 2022 May - "Cardiac arrest (CA) produces global ischemia/reperfusion injury resulting in substantial multiorgan damage ... Overall, as an effective and safe drug, metformin has the potential to be an easily translatable intervention for improving survival and preventing brain damage after CA" - See metformin at ReliableRX.
• The effects of metformin and forskolin on sperm quality parameters and sexual hormones in type II diabetic male rats - Andrologia 2022 Apr 8 - "Treating diabetic rats with metformin and forskolin resulted in significant improvement in sperm quality parameters, increased testosterone levels, reduced oxidative stress in blood and testicular tissue, and decreased blood sugar, and Bax to Bcl-2 ratio level. Although the combination of metformin with forskolin had a higher effect in some parameters such as testosterone levels compared to treatment with metformin or forskolin alone, this combination had not shown a synergistic effect in all the sperm quality parameters. Metformin and forskolin are effective anti-diabetic agents, which significantly improve the sperm quality and sexual hormone levels in diabetic rats. Combining metformin and gorskolin resulted in significantly better testosterone level and antioxidant activity in blood serum without significant effect on sperm quality of diabetic rats" - See metformin at ReliableRX and forskolin at Amazon.com.
• Metformin to treat Huntington disease: a pleiotropic drug against a multi-system disorder - Mech Ageing Dev 2022 Mar 30 - "Huntington disease (HD) is a neurodegenerative disorder produced by an expansion of CAG repeats in the HTT gene. Patients of HD show involuntary movements, cognitive decline and psychiatric impairment. People carrying abnormally long expansions of CAGs (more than 35 CAG repeats) produce mutant huntingtin (mHtt), which encodes tracks of polyglutamines (polyQs). These polyQs make the protein prone to aggregate and cause it to acquire a toxic gain of function. Principally affecting the frontal cortex and the striatum, mHtt disrupts many cellular functions ... Several studies reported that metformin, a widely-used anti-diabetic drug, is neuroprotective in models of HD ... Metformin is a pleiotropic drug, modulating different targets such as AMPK, insulin signalling and many others. These molecules regulate autophagy, chaperone expression, and more, which in turn reduce mHtt toxicity. Moreover, metformin alters gut microbiome and its metabolic processes"
• Metformin and the heart: Update on mechanisms of cardiovascular protection with special reference to comorbid type 2 diabetes and heart failure - Metabolism 2022 Feb 7 - "Recently, the position of metformin as first choice glucose-lowering agent has been supplanted to some extent by the emergence of newer classes of antidiabetic therapy, namely the sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. These agents have benefitted through support from large cardiovascular outcomes trials with more modern trial designs than earlier studies conducted to assess metformin. Nevertheless, clinical research on metformin continues to further assess its many potentially advantageous effects. Here, we review the evidence for improved cardiovascular outcomes with metformin in the context of the current era of diabetes outcomes trials. Focus is directed towards the potentially cardioprotective actions of metformin in patients with type 2 diabetes and heart failure (HF), now recognised as the most common complication of diabetes"
• Metformin induces S-adenosylmethionine restriction to extend the Caenorhabditis elegans healthspan through H3K4me3 modifiers - Aging Cell 2022 Feb 11 - "Metformin, a widely prescribed first-line drug for the treatment of type II diabetes mellitus, has been shown to extend lifespan and delay the onset of age-related diseases. The precisely mechanisms by which these effects are realized remain elusive ... Through genetic screening of C. elegans, we find that metformin promotes the healthspan through an H3K4 methyltransferase/demethylase complex to downregulate the targets, including mTOR and S6 kinase. Thus, our studies provide molecular links between meformin, SAM limitation, histone methylation, and healthspan and elucidate the mode action of metformin-regulated healthspan extension will boost its therapeutic application in the treatment of human aging and age-related diseases"
• Metformin alleviates the depression-like behaviors of elderly apoE4 mice via improving glucose metabolism and mitochondrial biogenesis - Behav Brain Res 2022 Jan 25 - "Apolipoprotein E4 (apoE4) is closely related to late-onset depression (LOD). In addition, the benefits of metformin treatment of depression have been documented in a range of rodent studies and human trials, but few studies have probed into the effect of metformin on and the related mechanism in depressed elderly mice, especially in those APOE4 carriers ... These data suggest that metformin ameliorates the depression-like behaviors probably by improving glucose metabolism and mitochondria biogenesis in the hippocampus of aged apoE4 mice. These findings imply that chronic metformin treatment can improve apoE4-mediated LOD, providing mechanistic insights for apoE4- and age-based depression prevention and therapy"
• Synergistic Effects of Combined Anthocyanin and Metformin Treatment for Hyperglycemia In Vitro and In Vivo - J Agric Food Chem 2022 Jan 19 - "These results suggest that the use of anthocyanins can enhance the efficacy of metformin treatment for hyperglycemia and provide a reference for further clinical research regarding nutrition and supplementary treatment" -  See metformin at ReliableRX and anthocyanins at Amazon.com.
• Metformin maintains intrahepatic triglyceride content through increased hepatic de novo lipogenesis - Eur J Endocrinol 2022 Jan 1 - "intrahepatic triglyceride (IHTG) ... hepatic de novo lipogenesis (DNL) and fatty acid (FA) oxidation ... Twelve weeks treatment with metformin resulted in a significant reduction in body weight and improved insulin sensitivity, but IHTG content and FA oxidation remained unchanged. Metformin treatment was associated with a significant decrease in VLDL-triglyceride (TG) concentrations and a significant increase in the relative contribution of DNL-derived FAs to VLDL-TG. There were subtle and relatively few changes in subcutaneous adipose tissue FA metabolism and the plasma metabolome with metformin treatment"
• Metformin ameliorates chronic colitis in a mouse model by regulating interferon-γ-producing lamina propria CD4 + T cells through AMPK activation - FASEB J 2022 Feb - "Metformin, a commonly prescribed drug for type 2 diabetes mellitus, has been shown to activate AMP-activated protein kinase (AMPK). Notably, AMPK activation has recently been observed to be associated with anti-inflammatory responses. Metformin is also reported to elicit anti-inflammatory responses in CD4+ T cells, resulting in improvement in experimental chronic inflammatory diseases, such as systemic lupus erythematosus ... metformin suppresses the frequency of interferon (IFN) -γ-producing LP CD4+ T cells in vitro, which were regulated by AMPK activation, a process possibly induced by the inhibition of oxidative phosphorylation. Furthermore, we examined the effects of metformin on an in vivo IBD model. Metformin-treated mice showed AMPK activation in LP CD4+ T cells and ameliorated colitis. Our study demonstrates that metformin-induced AMPK activation in mucosal CD4+ T cells contributes to the improvement of IBD by suppressing IFN-γ production. Moreover, our results indicate that AMPK may be a target molecule for the regulation of mucosal immunity and inflammation. Thus, AMPK-activating drugs such as metformin may be potential therapeutic agents for the treatment of IBD" - See metformin at ReliableRX.
• Metformin use is associated with a decrease in risk of hospitalization and mortality in COVID-19 diabetic patients: a population-based study in Lombardy - Diabetes Obes Metab 2022 Jan 10 - "In multivariable models metformin use was associated with a significantly lower risk of total mortality (OR 0.70; 95% CI 0.66-0.75), in-hospital mortality (OR 0.68; 95% CI 0.63-0.73), hospitalization for COVID-19 (OR 0.86; 95% CI 0.81-0.91) and ICU admission (OR 0.81; 95% CI 0.69-0.94) compared with metformin non-users. Results were similar in propensity score analysis; metformin was associated with significantly lower risk of total mortality (OR 0.79; 95% CI, 0.73-0.86), in-hospital mortality (OR 0.74; 95% CI, 0.67-0.81) and ICU admission (OR 0.77" - See metformin at ReliableRX.
• Metformin treatment of juvenile mice alters aging-related developmental and metabolic phenotypes - Mech Ageing Dev 2021 Nov 12 - "Accumulating evidence suggests that the influence on developmental traits might have long-term effects on aging and health later in life. Metformin is a widely used drug for treating type 2 diabetes and is also used for delaying sexual maturation in girls with precocious puberty ... Heterogeneous mice (UM-HET3) were treated with i.p. metformin between the ages of 15 and 56 days. Our results show that body weight and food consumption were increased in both sexes, and sexual maturation was delayed in females. Tail length and circulating insulin-like growth factor 1 (IGF1) levels were significantly increased in both sexes. No significant difference was found in insulin tolerance test, but glucose tolerance was significantly reduced in the males. Circulating adiponectin and insulin levels were altered by metformin treatment in a sex-specific manner. Analysis of quantitative insulin sensitivity check index (QUICKI) suggests that metformin treatment increased insulin sensitivity in female pups, but had opposite effect in male pups. This study revealed that early life metformin treatment alters development and metabolism of mice in both sex-specific and non-specific manners. These effects of metformin may have long-term impacts on aging-related traits"
  • Risk Factors for Sarcopenia in the Elderly with Type 2 Diabetes Mellitus and the Effect of Metformin - J Diabetes Research Oct 7 2020 - "Participants who took metformin alone or combined with other drugs exhibited a lower risk for sarcopenia than those who took no medication (, 95% –0.904 and , 95% –0.702, respectively; ) ... Conclusions. We showed that being female and at an older age, lower educational level, and lower BMI were risk factors for sarcopenia in elderly T2DM and that metformin acted as a protective agent against sarcopenia in these patients" - See metformin at ReliableRX.
• Metformin induces muscle atrophy by transcriptional regulation of myostatin via HDAC6 and FoxO3a - J Cachexia Sarcopenia Muscle 2021 Nov 2 - "Our results demonstrate that metformin treatment impairs muscle function through the regulation of myostatin in skeletal muscle cells via AMPK-FoxO3a-HDAC6 axis. The muscle-wasting effect of metformin is more evident in WT than in db/db mice, indicating that more complicated mechanisms may be involved in metformin-mediated muscular dysfunction"
• The effects of co-administration of artichoke leaf extract supplementation with metformin and vitamin E in patients with nonalcoholic fatty liver disease: A randomized clinical trial - Phytother Res 2021 Sep 17 - "Medicinal plants are widely used as a complementary therapy to treat complex diseases, such as nonalcoholic fatty liver disease (NAFLD). Therefore, this study was done to investigate the effect of co-administration of artichoke leaf extract supplement (ALES) with conventional medicines on patients with NAFLD ... In summary, the results of the present study showed that the concomitant use of ALES with metformin and vitamin E can have beneficial effects on amelioration of complications in patients with NAFLD" - See artichoke extract at Amazon.com, vitamin E at Amazon.com and iHerb and metformin at ReliableRX.
• Potential Interaction of Fresh Garlic with Metformin during Ischemia-Reperfusion Induced Cardiac Injury in Diabetic Rats - Evid Based Complement Alternat Med 2021 Sep 4 - "The combined therapy of MET and garlic provided synergistic cardioprotection, implying that garlic seems to possess promise in lowering toxic parameters by protecting diabetic induced myocardial injury" - See garlic supplements at Amazon.com and garlic at iHerb.com and metformin at ReliableRX.
• Metformin ameliorates maternal high-fat diet-induced maternal dysbiosis and fetal liver apoptosis - Lipids Health Dis 2021 Sep 8 - "The deleterious effect of maternal high-fat diet (HFD) on the fetal rat liver may cause later development of non-alcoholic fatty liver disease (NAFLD) ... This study demonstrated the beneficial effects of prenatal metformin on maternal liver steatosis, focusing on the gut-liver axis. In addition, the present study indicates that prenatal metformin could ameliorate maternal HFD-induced inflammation and apoptosis in the fetal liver and intestines"
• Management of Cognitive Dysfunction - The journal of nutrition, health & aging volume 25, pages819–820 (2021) - "The first of the nootropics introduced to treat dementia was the ergotoxine derivative, hydergine. A meta-analysis found that hydergine significantly improved cognition based on global ratings (8). However, these effects were considered to be modest ... Recently, our group has shown in an epidemiological study that the tetanus, diphtheria, pertussis (Tdap) vaccine markedly reduces dementia in persons receiving it compared to unvaccinated individuals (14). This may be because of activation of regulatory T cells. This effect is much greater than seen with the available drugs for the treatment of dementia ... Metformin in persons with Type 2 diabetes mellitus reduces dementia (17, 18). The prevalence of dementia has been reduced in the USA over the last decade, most probably due to the treatment of hypertension ... Most importantly, there are a number of nutritional and psychological interventions that appear to reduce dementia (Table 2). These include especially fruit and vegetable diets such as the Mediterranean (21) or the MIND diets (22). Extra virgin olive oil further decreases the chance of developing cognitive dysfunction by reducing inflammatory damage in the brain (23, 24). There is some evidence that yogurt (25) and curcumin (26) may also decrease the development of cognitive dysfunction. Oligomannate, which is derived from seaweed, decreases microbiome inflammatory response similar to yogurt and improves cognition" - See metformin at ReliableRX and oligomannate at Amazon.com.
• Metformin and leucine increase satellite cells and collagen remo - FASEB J 2021 Sep;35(9):e21862 - "Loss of muscle mass and strength after disuse followed by impaired muscle recovery commonly occurs with aging. Metformin (MET) and leucine (LEU) individually have shown positive effects in skeletal muscle during atrophy conditions but have not been evaluated in combination nor tested as a remedy to enhance muscle recovery following disuse atrophy in aging ... Together, the dual treatment of MET and LEU was able to increase muscle function, satellite cell content, and reduce collagen accumulation, thus improving muscle quality during disuse and recovery in aging" - See metformin at ReliableRX and leucine products at Amazon.com and leucine at iHerb.
• ATXN7L3B promotes hepatocellular carcinoma stemness and is downregulated by metformin - Biochem Biophys Res Commun 2021 Aug 6 - "Hepatocellular carcinoma (HCC) is the major cause of liver cancer-associated morality. Metformin, used for treating type 2 diabetes, has antitumor activity and reduces the risk of some diabetes-related tumors, such as liver and breast cancer ... metformin reduced ATXN7L3B level in HCC cells. ATXN7L3B expression was significantly negatively correlated with survival in liver cancer patients. We also demonstrated that ATXN7L3B promoted HCC stemness. Metformin treatment decreased ATXN7L3B-induced tumor-initiating ability in a HCC mouse model, implying that metformin may inhibit cancer stemness by downregulating ATXN7L3B. Our study supports the antitumor activity of metformin and its potential as an anticancer drug for HCC treatment" - See metformin at ReliableRX.
• Metformin reduces oxandrolone- induced depression-like behavior in rats via modulating the expression of IL-1β, IL-6, IL-10 and TNF-α - Behav Brain Res 2021 Jul 17 - "Oxandrolone (OXA) is an androgen and anabolic steroid (AAS) that is used to reverse weight loss associated with some medical conditions. One of the side effects of OXA is its potential to induce depressive symptoms. Growing evidence suggested that neuroinflammation and cytokines play crucial roles in sickness behavioral and associated mood disturbances. Previous studies showed that metformin attenuated neuroinflammation. This study investigated the potential protective role of metformin against OXA-induced depression-like behavior and neuroinflammation ... oxandrolone induced depression-like behavior and dysregulated pro-/anti-inflammatory cytokines, while metformin attenuated these effects. These findings suggest that metformin is a potential treatment to reverse the depressive effects induced by oxandrolone that involve neuroinflammatory effects"
• The effect of metformin on mortality and severity in COVID-19 patients with diabetes mellitus - Diabetes Res Clin Pract 2021 Jul 21 - "metformin was associated with significantly decreased mortality and severity in COVID-19 patients with diabetes (OR = 0.64, 95% CI = 0.51 - 0.79 for mortality, and OR = 0.81, 95% CI = 0.66 - 0.99 for severity)" - See metformin at ReliableRX.
• Metformin improved memory impairment caused by chronic ethanol consumption during adolescent to adult period of rats: Role of oxidative stress and neuroinflammation - Behav Brain Res 2021 Jun 1 - "Adolescence is a crucial time for brain maturation. We investigated the protective effects of metformin (Met) on behavioral changes, oxidative stress, tumor necrosis factor alpha (TNF-α) and nitrite in adulthood induced by ethanol (Eth) consumption during adolescent to adult period of rats ... Our findings showed that the protective effects of Met against chronic Eth consumption induced learning and memory impairment were accompanied by decreasing of TNF-a, nitrite and oxidative stress in adolescent rats"
• Long-Term Administration of Metformin Ameliorates Age-Dependent Oxidative Stress and Cognitive Function in Rats - Behav Brain Res 2021 May 6 - "Recently, metformin, as the first-line treatment for type II diabetes, has been shown to increase the life expectancy of diabetic patients ... 32 normal male Wistar rats were randomly assigned into control and metformin groups ... It can be concluded that long-term metformin intake, by modulating the oxidant/antioxidant mechanisms, prevents the loss of hippocampal neurons caused by age-dependent oxidative stress and improves memory"
• Metformin extended-release versus metformin immediate-release for adults with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials - Diabetes Res Clin Pract 2021 Apr 19 - "MIR was statistically associated with better HbA1c lowering (MD 0.09% [0.01%, 0.17%]) and serum lipid control, and MXR only with reduced dyspepsia (RR 0.58 [0.34, 0.98]). MXR and MIR were similar in other considered outcomes ... Conclusions: MXR was associated with statistically worse but likely clinically insignificant HbA1c lowering, similar plasma glucose control, and minimal improvement of metformin intolerance versus MIR"
• Metformin and cancer-specific survival among breast, colorectal, or endometrial cancer patients: a nationwide data linkage study - Diabetes Res Clin Pract 2021 Apr 6 - "The 1-year adherence was similar at baseline in three cohorts, on average 75%. Each 10% increase in 1-year adherence to metformin reduced cancer-specific mortality among women with breast cancer (adjusted HR=0.95; 95% CI, 0.93-0.97), colorectal cancer (adjusted HR=0.94; 95% CI, 0.91-0.96), or endometrial cancer (adjusted HR=0.95; 95% CI, 0.90-0.99). The inverse associations remained unchanged in most subgroup analyses"
• Gut microbiota compositions and metabolic functions in type 2 diabetes differ with glycemic durability to metformin monotherapy - Diabetes Res Clin Pract 2021 Mar 4 - "Metformin, the first-line treatment for type 2 diabetes, has been found to modulate the gut microbiota ... There were different compositions of gut microbiota with unique microbial metabolic pathways between type 2 diabetes with and without glycemic durability to metformin monotherapy. Microbial salvage by increasing thiamine biosynthesis might be beneficial for the metformin durable group to maintain optimal glycemic control"
• The Effect of Metformin vs Placebo on Sex Hormones in Canadian Cancer Trials Group MA.32 - J Natl Cancer Inst 2021 Feb 1 - "Metformin has been associated with lower breast cancer (BC) risk and improved outcomes in observational studies. Multiple biologic mechanisms have been proposed, including a recent report of altered sex hormones ... Metformin lowered estradiol levels, independent of BMI. This observation suggests a new metformin effect that has potential relevance to estrogen sensitive cancers" - Note: Metformin and also coffee, increase SHBG.  You might be able to counter it with Tongkat ali, boron, DHEA, vitamin D and/or fish oil.
• Combination of metformin and RG7388 enhances inhibition of growth and induction of apoptosis of ovarian cancer cells through the PI3K/AKT/mTOR pathway - Biochem Biophys Res Commun 2020 Oct 10 - "reactive oxygen species (ROS) ... The combination of MET and RG7388 significantly increased growth inhibition, apoptosis, and ROS of A2780 and SKOV3 cells compared with either agent alone. Additionally, in vitro and in vivo results showed that MET and/or RG7388 inhibited the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway and their combination had a stronger effect. Our findings suggest that the combination of MET and RG7388 enhances growth inhibition and apoptosis induction of ovarian cancer cells through the PI3K/AKT/mTOR pathway and accumulation of intracellular ROS."
• Metformin ameliorates skeletal muscle atrophy in Grx1 KO mice by regulating intramuscular lipid accumulation and glucose utilization - Biochem Biophys Res Commun 2020 Oct 14 - "Disorder in lipid metabolism and glucose utilization could impair the quality and function of skeletal muscle. Glutaredoxin-1 (Grx1) acts as a vital metabolic regulator of redox homeostasis ... intraperitoneal injection of metformin for 15 consecutive days ameliorated skeletal muscle atrophy caused by Grx1 deficiency to a certain extent. Taken together, these findings indicate that Grx1 deficiency might induce skeletal muscle atrophy by regulating the intramuscular lipid deposition and glucose utilization, which could be attenuated by metformin. Therefore, the expression or activity of Grx1 may be a pharmacological approach to ameliorate muscle atrophy diseases, such as sarcopenia" - See metformin at ReliableRX.
• Metformin use in elderly population with diabetes reduced the risk of dementia in a dose-dependent manner, based on the Korean NHIS-HEALS cohort - Diabetes Res Clin Pract 2020 Oct 14 - "Participants were divided into five groups: metformin non-users with diabetes mellitus (DM), metformin users with DM (low-, mid-, and high-users), and non-diabetic Individuals ... The median follow-up was 12.4 years. The overall incidence rate of dementia was 11.3% (8.4% in men and 13.9% in women). Compared with metformin non-users, hazard ratios (95% confidence intervals) of low-, mid-, and high-users and non-diabetic individuals for dementia were 0.97 (0.73-1.28), 0.77 (0.58-1.01), 0.48 (0.35-0.67), and 0.98 (0.84-1.15), respectively, in men, respectively, and 0.90 (0.65-0.98), 0.61 (0.50-0.76), 0.46 (0.36-0.58), and 0.92 (0.81-1.04), respectively, in women, after full adjustment of confounding variables" - See metformin at ReliableRX.
• The effect of metformin treatment on the basal and gonadotropin-stimulated steroidogenesis in male rats with type 2 diabetes mellitus - Andrologia 2020 Sep 20 - "We concluded that metformin treatment normalises the testicular steroidogenesis in diabetic rats, which is due to restoration of the gonadotropin and leptin systems in the testes and is associated with an improvement in spermatogenesis" - See metformin at ReliableRX.
• Different effects of metformin on hypothalamic-pituitary-thyroid axis activity in levothyroxine-treated and levothyroxine-naïve women with non-autoimmune hypothyroidism - J Clin Pharm Ther 2020 Aug 21 - "Thirty-two women (16 in each treatment arm) completed the study. At baseline, both groups differed only in free and total thyroxine levels. Metformin reduced glucose levels and glycated haemoglobin, improved insulin sensitivity and decreased thyrotrophin levels. The impact on insulin sensitivity and thyrotrophin was stronger in women simultaneously treated with levothyroxine than in women not receiving this hormone. In levothyroxine-treated patients, metformin slightly reduced prolactin levels. In both study groups, metformin treatment exerted a neutral effect on free and total thyroxine and triiodothyronine. The thyrotrophin-lowering effect of metformin correlated with the improvement in insulin sensitivity and in levothyroxine-treated women with the changes in prolactin levels ... The obtained results suggest that metformin/levothyroxine combination therapy may be an interesting treatment option in women with non-autoimmune hypothyroidism poorly tolerating high-dose levothyroxine treatment" - See metformin at ReliableRX.
• Combination of Curcumin and Metformin Inhibits Cell Growth and Induces Apoptosis without Affecting the Cell Cycle in LNCaP Prostate Cancer Cell Line - Nutr Cancer 2020 Jul 13 - "The viability of cells treated with curcumin, metformin, and their combination was significantly (P < 0.05) reduced with increasing the concentration and prolonging the treatment time. Meanwhile, the combination showed a synergistic effect within 48 h. In the curcumin treated group, the expression of Bcl-2 and hTERT genes diminished. In the metformin treated group, the expression of Bax and PUMA genes was enhanced while the expression of Bcl-2, hTERT, mTOR, and p53 genes declined. Although all treatments induced apoptosis, the combination of curcumin and metformin showed the maximum level of apoptosis, cytotoxicity, and expression of Bax gene. The combination of curcumin and metformin showed synergistic effects within 48 h. This combination could be a potential therapeutic candidate for prostate cancer to be further investigated" - See curcumin at Amazon.com and iHerb and metformin at ReliableRX.
• A Proposed Mechanism for the Possible Therapeutic Potential of Metformin in COVID-19 - Diabetes Res Clin Pract 2020 Jun 24 - "The whole world is facing a tough time these days struggling against the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is not any specific effective drug for this viral infection. Thus, we are trying to treat patients with non-specific drug cocktails. Metformin, as a strong base, a potential regulator of Vacuolar ATPase (V-ATPase) and endosomal Na+/H+ exchangers (eNHEs), additionally a regenerative agent for lung fibrosis, seems to be beneficial for patients in acute, chronic and recovery phases of COVID-19"
• Metformin Inhibits Intracranial Aneurysm Formation and Progression by Regulating Vascular Smooth Muscle Cell Phenotype Switching via the AMPK/ACC Pathway - J Neuroinflammation 2020 Jun 16 - "vascular smooth muscle cell (VSMC) ... intracranial aneurysm (IA) ... Metformin protects against IA formation and rupture by inhibiting VSMC phenotype switching and proliferation, migration, and apoptosis. Thus, metformin has therapeutic potential for the prevention of IA" - ReliableRXPharmacy carries metformin.
  • Intracranial aneurysm - Wiki - "Intracranial aneurysm, also known as brain aneurysm, is a cerebrovascular disorder in which weakness in the wall of a cerebral artery or vein causes a localized dilation or ballooning of the blood vessel"
• Metformin in COVID-19: A Possible Role Beyond Diabetes - Diabetes Res Clin Pract. 2020 Apr 29 - "The mammalian target of rapamycin (mTOR) signalling plays an important role in the pathogenesis of influenza, besides modulating antibody response for cross-protective immunity against infective influenza viruses. Metformin activates AMPK via liver kinase B1 (LKB1), inhibiting the mTOR pathway. It also indirectly attenuates AKT activation through phosphorylation of insulin receptor substrate 1 (IRS-1) resulting in inhibition of the mTOR signalling cascade [11]. Other biguanide molecules, buformin and phenformin have been associated with better survival outcomes in animal models of influenza [12,13]. Further, the PI3K/AKT/mTOR pathway plays major roles in MERS CoV infection [14]. Since metformin inhibits the same pathway, it would be interesting to decipher its role against SARS-CoV-2"
• Effects of metformin on lifespan, cognitive ability and inflammatory response in a short-lived fish - J Gerontol A Biol Sci Med Sci. 2020 May 3 - "Metformin, an oral antidiabetic drug, prolongs the lifespan in nematode, silkworm and other transgenic rodents, but its effects on longevity and aging-related cognitive ability using natural aging vertebrate models remain poorly understood ... Total of 145 fish, 72 fish were fed with metformin in the concentration of 2mg/gram food and 73 fish without metformin from 16 weeks of age until the end of their lives. The chronic feeding with metformin prolonged the lifespan of the fish and delayed aging with retarded accumulation of lipofuscin in liver, senescence-associated beta-galactosidase (SA-β-gal) activity in skin and serum levels of cholesterol and triglyceride significantly in the fish at 10-month-old. Furthermore, metformin improved motor, learning and memory skills by behavior tests accompanying with reduction of SA-β-gal activity and neurofibrillary degeneration and inhibition of inflammatory response including down-regulated NF-κB and pro-inflammatory cytokines IL-8, TNF-α and IL-1β expression and enhanced anti-inflammatory cytokine IL-10 level in brain. These findings demonstrate that metformin prolongs the lifespan and exerts neuroprotective and anti-inflammation function to improve cognitive ability in annual fish. It might be an effective strategy by using metformin to raise the possibility of promoting healthy aging of old population in aging process" - See metformin at ReliableRxPharmacy.
• Postdiagnostic Metformin Use and Survival of Patients With Colorectal Cancer: A Nationwide Cohort study - Int J Cancer. 2020 Mar 20 - "After adjustment for demographic and clinical covariates, metformin users had lower all-cause mortality than did nonusers (hazard ratio [HR], 0.42; 95% CI, 0.40-0.44) and lower CRC-specific mortality (HR, 0.41; 95% CI, 0.39-0.44). Similar but somewhat attenuated effects were observed after stabilized IPTW (HR for all-cause mortality, 0.56; 95% CI, 0.53-0.59; HR for CRC-specific mortality, 0.58; 95% CI, 0.55-0.61). Similar results were observed in stratified analyses of 2,112 patients with no prediagnostic metformin use and 14,564 patients with prediagnostic metformin use. Findings for both outcomes were consistent in multiple sensitivity analyses. Use of postdiagnostic metformin was associated with significantly lower all-cause mortality and CRC-specific mortality, regardless of prior metformin use. These findings support the use of metformin as an adjunct to standard care of diabetic patients with CRC" - See metformin at ReliableRX.
• Preventative effects of metformin on glucocorticoid-induced osteoporosis in rats - J Bone Miner Metab. 2019 Sep - "These findings suggest that metformin prevents GC-induced bone loss by suppressing bone resorption and stimulating bone formation in trabecular bone. The action mode of metformin was different from alendronate, which only suppressed bone resorption"
• Metformin reduces risk of varicose veins in type 2 diabetes patients - Diabetes Metab Res Rev. 2019 Jul 19:e3206 - "The hazard ratio for ever versus never users in the unmatched cohort was 0.57 (95% confidence interval: 0.47-0.69); and was 0.60 (0.45-0.80) for the matched cohort. In the unmatched cohort, the hazard ratios for the first, second and third tertiles of cumulative duration were 1.03 (0.83-1.28), 0.55 (0.44-0.69) and 0.29 (0.23-0.37), respectively. The respective hazard ratios in the matched cohort were 0.97 (0.65-1.43), 0.79 (0.55-1.15) and 0.24 (0.13-0.42) ... Metformin use is associated with a lower risk of varicose veins in type 2 diabetes patients"
• Metformin exposure and survival in head and neck cancer: A large population-based cohort study - J Clin Pharm Ther. 2019 Aug;44(4):588-594 - "In the covariate-adjusted model, the all-cause mortality rate appeared lower (HR: 0.81, 95% CI: 0.61-1.09) among metformin exposed patients during the 2 years post-diagnosis, while the all-cause mortality rate appeared higher (HR: 1.20, 95% CI: 0.94-1.53) among exposed patients after 2 years post-diagnosis. Metformin was protective among patients ≤60 years of age (HR for the period of 0-2 years post-diagnosis: 0.22, 95% CI 0.09-0.56; HR for the period ≥2 years post-diagnosis: 0.56, 95% CI 0.26-1.22) but not in those >60 years ... In this population-based study of metformin in HNC, we found a modest protective association between metformin exposure and all-cause mortality in the 2-year post-diagnosis period. Age appeared to modify the association between metformin and HNC survival."
• Inulin and metformin ameliorate polycystic ovary syndrome via anti-inflammation and modulating gut microbiota in mice - Endocr J. 2019 Jul 3 - "Mice were divided into 4 groups: control group (CON), model group (MOD), inulin group (INU), metformin group (MET). The last three groups were fed 6 mg of dehydroepiandrosterone (DHEA) per 100 g body weight and 60% high-fat diet to generate mice model. After 21 days of intervention, mice were euthanized and associated indications were investigated. Body weight (BW) and testosterone (T) levels were significantly decreased, but estradiol (E2) levels were increased in INU or MET group, respectively. Ovary HE staining demonstrated that inulin or metformin ameliorated PCOS morphology. Inflammatory indicators from plasma and ovary including TNF-α, IL-6, and IL-17A were decreased in INU or MET group. Moreover, IL-10 in ovary of INU or MET group was increased. Sequencing and analysis of gut microbiota showed that compared to MOD group, Bifidobacterium was increased, but Proteobacteria, Helicobacter and Parasutterella were decreased in INU group. Helicobacter was decreased in MET group. Correlation analysis showed that gut microbiota was correlated with inflammatory factors. Our results revealed that inulin and metformin alleviated PCOS via anti-inflammation and modulating gut microbiota, which may contribute to potential clinical therapy for the disease" - See inulin at Amazon.com.
• The use of metformin, insulin, sulphonylureas, and thiazolidinediones and the risk of fracture: Systematic review and meta-analysis of observational studies - Obes Rev. 2019 Jun 28 - "A random effects model was used to estimate the summary relative risks (RRs) with 95% confidence intervals (CIs). The use of insulin (RR 1.49, 95% CI 1.29, 1.73; n = 23 studies), sulphonylureas (RR 1.30, 95% CI 1.18, 1.43; n = 10), and thiazolidinediones (RR 1.24, 95% CI 1.13, 1.35; n = 14) was associated with an increased risk of fracture, whereas the use of metformin was associated with a reduced risk of fracture (RR 0.86, 95% CI 0.75, 0.99; n = 12). Regarding types of thiazolidinediones, both pioglitazone (RR 1.38, 95% CI 1.23, 1.54; n = 5) and rosiglitazone (RR 1.34, 95% CI 1.14, 1.58; n = 5) were positively associated with the risk of fracture"
• Metformin protects bone mass in ultra-high-molecular-weight polyethylene particle-induced osteolysis by regulating osteocyte secretion - J Bone Miner Metab. 2019 May;37(3):399-410 - "Our finding suggests that metformin induces differentiation and mineralization of osteoblasts, while inhibits osteoclastogenesis via mature osteocytes secretion. Therefore, the drug might be beneficial for not only diabetes but also in other bone disorders by acting on mature osteocytes"
• Conflicting studies in the same publication within two weeks of each other:
  • Metformin Improves Learning and Memory in the SAMP8 Mouse Model of Alzheimer's Disease - J Alzheimers Dis. 2019 Apr 3 - "A pilot clinical study found cognitive improvement with metformin in patients with mild cognitive impairment (MCI). Preclinical studies suggest metformin reduces Alzheimer-like pathology in mouse models of Alzheimer's disease (AD). In the current study, we used 11-month-old SAMP8 mice. Mice were given daily injections of metformin at 20 mg/kg/sc or 200 mg/kg/sc for eight weeks. After four weeks, mice were tested in T-maze footshock avoidance, object recognition, and Barnes maze. At the end of the study, brain tissue was collected for analysis of PKC (PKCζ, PKCι, PKCα, PKCγ, PKCɛ), GSK-3β, pGSK-3βser9, pGSK-3βtyr216, pTau404, and APP. Metformin improved both acquisition and retention in SAMP8 mice in T-maze footshock avoidance, retention in novel object recognition, and acquisition in the Barnes maze. Biochemical analysis indicated that metformin increased both atypical and conventional forms of PKC; PKCζ, and PKCα at 20 mg/kg. Metformin significantly increased pGSK-3βser9 at 200 mg/kg, and decreased Aβ at 20 mg/kg and pTau404 and APPc99 at both 20 mg/kg and 200 mg/kg. There were no differences in blood glucose levels between the aged vehicle and metformin treated mice. Metformin improved learning and memory in the SAMP8 mouse model of spontaneous onset AD. Biochemical analysis indicates that metformin improved memory by decreasing APPc99 and pTau. The current study lends support to the therapeutic potential of metformin for AD"
  • Metformin Therapy Aggravates Neurodegenerative Processes in ApoE- /- Mice - J Alzheimers Dis. 2019 Mar 19 - "this study supports previous observations showing that metformin causes impairment of cognition"
• Metformin Attenuates Early-Stage Atherosclerosis in Mildly Hyperglycemic Oikawa-Nagao Mice - J Atheroscler Thromb. 2019 Apr 11 - "(Oikawa-Nagao Diabetes-Prone [ON-DP] and -Resistant [ON-DR]) ... Mildly hyperglycemic ON-DP and normoglycemic ON-DR female mice fed an atherogenic diet for 20 weeks (8-28 weeks of age). During the feeding period, one group of each mouse line received metformin in drinking water (0.1%), while another group received water alone as control ... metformin treatment significantly reduced atherosclerotic lesion formation in the ON-DP mice (59% of control), whereas no significant effect of metformin was observed in the lesion size of the ON-DR mice ... Metformin can attenuate early-stage atherogenesis in mildly hyperglycemic ON-DP mice. Pleiotropic effects of metformin, beyond its glucose-lowering action, may contribute to the antiatherogenic property in the early-stage atherosclerosis" - See metformin at the Antiaging Store.
• Metformin Improves Learning and Memory in the SAMP8 Mouse Model of Alzheimer's Disease - J Alzheimers Dis. 2019 Apr 3 - "Diabetics are at an increased risk of developing dementia. Recent epidemiological studies suggest that metformin treatment prevents cognitive decline in diabetics ... Preclinical studies suggest metformin reduces Alzheimer-like pathology in mouse models of Alzheimer's disease (AD). In the current study ... Metformin significantly increased pGSK-3βser9 at 200 mg/kg, and decreased Aβ at 20 mg/kg and pTau404 and APPc99 at both 20 mg/kg and 200 mg/kg ... Metformin improved learning and memory in the SAMP8 mouse model of spontaneous onset AD. Biochemical analysis indicates that metformin improved memory by decreasing APPc99 and pTau"
• Survival Benefit of Metformin Adjuvant Treatment For Pancreatic Cancer Patients: a Systematic Review and Meta-Analysis - Cell Physiol Biochem 2018;49:837–847 - "The current systematic review and meta-analysis based on 17 studies involving 36791 patients suggests that pancreatic cancer patients with metformin adjuvant treatment may have a prolonged survival compared with those not receiving metformin, though there is evidence of moderate heterogeneity across studies" - See metformin at ReliableRX..
• Metformin and risk of developing nasopharyngeal cancer in patients with type 2 diabetes mellitus - Metabolism. 2018 May 2 - "Metformin use is associated with a significantly lower risk of NPC"
• Mortality Associated with Metformin Versus Sulfonylurea Initiation: A Cohort Study of Veterans with Diabetes and Chronic Kidney Disease - J Gen Intern Med. 2017 Nov 27 - "Initiation of metformin versus a sulfonylurea among individuals with type 2 diabetes and CKD was associated with a substantial reduction in mortality, in terms of both relative and absolute risk reduction"
• Towards natural mimetics of metformin and rapamycin - Aging (Albany NY). 2017 Nov 15 - "The analysis revealed many novel candidate metformin and rapamycin mimetics, including allantoin and ginsenoside (metformin), epigallocatechin gallate and isoliquiritigenin (rapamycin), and withaferin A (both)" - [Nutra USA] - See ginseng at Amazon.com and ashwagandha at Amazon.com.  See metformin at the Antiaging Store.
  • Withaferin A - wikipedia.org - "Withaferin A is a steroidal lactone, derived from Acnistus arborescens,[1] Withania somnifera[2] (Indian Winter cherry or Ashwagandha in Sanskrit) and other members of Solanaceae family"
• Association Between Metformin Adherence and All-Cause Mortality Among New Users of Metformin: A Nested Case-Control Study - Ann Pharmacother. 2017 Nov 1 - "Analyses revealed decreased mortality risks after long-term adherence to metformin. Specifically, RRs were 0.84 (95% CI = [0.71-0.98]) and 0.69 [0.57-0.85] after 4 to 6 and ��6 years of adherence to metformin, respectively. Survival benefits of long-term adherence (≥4 years) were also observed across most subgroups and particularly in patients using neither antihypertensive/cardiovascular drugs nor statins (0.57 [0.41-0.77])" - See metformin at the Antiaging Store.
• Metformin vs sulfonylurea use and risk of dementia in US veterans aged ��65 years with diabetes - Neurology. 2017 Sep 27 - "Crude hazard ratio [HR] for any dementia in metformin vs sulfonylurea users was 0.67 (95% confidence interval [CI] 0.61-0.73) and 0.78 (95% CI 0.72-0.83) for those <75 years of age and ≥75 years of age, respectively ... After accounting for confounding by indication, metformin was associated with a lower risk of subsequent dementia than sulfonylurea use in veterans <75 years of age"
• Metformin Has Positive Therapeutic Effects in Colon Cancer and Lung Cancer - Am J Med Sci. 2017 Sep;354(3):246-251 - "Metformin (MF), a diabetic drug, has antineoplastic activity as adjuvant therapy for breast cancer and prostate cancer. MF is thought to work via inhibition of mammalian target of rapamycin and activation of p53 and liver kinase B1 via adenosine 5'-monophosphate-activated protein kinase ... For CC, the MF group noted fewer deaths (48% versus 76%, P < 0.001), recurrences (4% versus 19%, P = 0.002), metastases (23% versus 46%, P = 0.001), better 5-year survival rates (57% versus 37%, P = 0.004), overall survival years (5.7 versus 4.1, P = 0.007) and greater carcinoembryonic antigen decrease (72% versus 47%, P = 0.015). MF was associated with improved 5-year survival rates (29% versus 15%, P = 0.023) and overall survival years (3.4 versus 1.8, P < 0.001) in LC"
• Metformin effects on the heart and the cardiovascular system: A review of experimental and clinical data - Nutr Metab Cardiovasc Dis. 2017 May 10 - "At the cellular level metformin's produces both AMP-activated kinase (AMPK) dependent and independent effects. At the systemic level, possibly also through other pathways, this drug improves endothelial function, protects from oxidative stress and inflammation, and from the negative effects of angiotensin II. On the myocardium it attenuates ischemia-reperfusion injury and prevents adverse remodeling induced by humoral and hemodynamic factors. The effects on myocardial cell metabolism and contractile function being not evident at rest or in more advanced stages of cardiac dysfunction, could be relevant during transient ischemia, during an acute increase in workload and in the early stages of diabetic/hypertensive cardiomyopathy as confirmed by few small clinical trials and some observational studies. The overall evidence emerging from both clinical trials and real world registry is in favor of a protective effect of metformin with respect to both coronary events and progression to heart failure"
• Effect of Long-term Metformin and Lifestyle in the Diabetes Prevention Program and its Outcome Study on Coronary Artery Calcium - Circulation. 2017 May 5 - "coronary artery calcium (CAC) ... CAC severity and presence were significantly lower among men in the metformin versus the placebo group (age-adjusted mean CAC severity: 39.5 vs 66.9 AU, p=0.04; CAC presence: 75% vs 84%, p=0.02), but no metformin effect was seen in women"
• Differential effects of metformin on age related comorbidities in older men with type 2 diabetes - J Diabetes Complications. 2017 Jan 28 - "age-related comorbidity (ARC) ... frailty-related diseases (FRD) ... 'Healthy Class' (53.6%): metformin reduced likelihoods of all ARCs (from 0.14% in dementia to 6.1% in CVD). 'High Cancer Risk Class' (11.6%): metformin reduced likelihoods of CVD (13.3%), cancer (45.5%), depression (5.0%), and FRD (13.7%). 'High CVD Risk Class' (17.4%): metformin reduced likelihoods of CVD (48.6%), cancer (3.2%), depression (2.8%), and FRD (6.3%). 'High Frailty Risk Class' (17.2%): metformin reduced likelihoods of CVD (18.8%), cancer (3.9%), dementia (3.8%), depression (15.6%), and FRD (23.8%)"
• Metformin inhibits castration-induced EMT in prostate cancer by repressing COX2/PGE2/STAT3 axis - Cancer Lett. 2016 Dec 30;389:23-32 - "We propose that metformin represses prostate cancer EMT and metastasis through targeting the COX2/PGE2/STAT3 axis. These findings suggest that metformin by itself or in combination with other anticancer drugs could be used as an anti-metastasis therapy"
• Effects of metformin on blood pressure in nondiabetic patients: a meta-analysis of randomized controlled trials - J Hypertens. 2016 Sep 7 - "Pooled results showed that metformin had a significant effect on SBP (mean difference -1.98 mmHg; 95% confidence interval -3.61, -0.35; P = 0.02), but not on DBP (mean difference -0.67 mmHg; 95% confidence interval -1.74, 0.41; P = 0.22). In subgroup analysis, we found that the effect of metformin on SBP was significant in patients with impaired glucose tolerance or obesity (BMI ≥30 kg/m), with a mean reduction of 5.03 and 3.00 mmHg, respectively"
• Activation of the AMPK/Sirt1 pathway by a leucine-metformin combination increases insulin sensitivity in skeletal muscle, and stimulates glucose and lipid metabolism and increases life span in Caenorhabditis elegans - Metabolism. 2016 Jul 9 - "We have previously shown leucine (Leu) to activate Sirt1 by lowering its KM for NAD+, thereby amplifying the effects of other sirtuin activators and improving insulin sensitivity. Metformin (Met) converges on this pathway both indirectly (via AMPK) and by direct activation of Sirt1 ... Leu and Met synergize to enable Sirt1 activation at low NAD+ concentrations (typical of energy replete states). Sirt1 and AMPK activations are required for Met-Leu's full action, which result in improvements in energy metabolism and insulin sensitivity" - See BulkSupplements Pure L-Leucine Powder (1 Kilogram) and metformin at The Antiaging Store.
• Metformin increases cortisol regeneration by 11βHSD1 in obese men with and without type 2 diabetes mellitus - J Clin Endocrinol Metab. 2016 Jul 26 - "Metformin increases whole body cortisol generation by 11βHSD1 probably through an indirect mechanism, potentially offsetting other metabolic benefits of metformin"
• The Effects of Pycnogenol® as Add-on Drug to Metformin Therapy in Diabetic Rats - Phytother Res. 2016 May 11 - "Pycnogenol® (PYC) belongs to strong antioxidants that may interfere with different pathways playing an important role in diseases associated with oxidative stress. Metformin (MET), commonly used antidiabetic drug, has cardio-protective effects via activation of AMP kinase (AMPK). In our study, we examined the effects of PYC as add-on drug to metformin therapy in streptozotocin (STZ)-induced diabetic rats. Our results revealed that both used agents, PYC and MET, showed improvement of blood glucose levels, vascular reactivity, left ventricular hypertrophy, expression of AMPK, glucose transporter 4 (GLUT4) and calcium/calmodulin-dependent protein kinase II (CaMKII) in left ventricle of the hearts. However, the combination of these interventions has failed to possess higher efficacy" - See Pycnogenol at Amazon.com.
• Metformin Has a Positive Therapeutic Effect on Prostate Cancer in Patients With Type 2 Diabetes Mellitus - Am J Med Sci. 2016 Apr;351(4):416-9 - "Patients with prostate cancer along with DM2 who remained on metformin were compared with controls who were not on metformin matched by age, weight, race and Gleason score cancer staging ... There were significantly fewer deaths (23% versus 10%), fewer recurrences (15% versus 8%), fewer metastases (5% versus 0%) and fewer secondary cancers (17% versus 6%) in the metformin group (P < 0.004). The final PSA value was lower in the metformin-treated group with a result approaching significance" - See metformin at The Antiaging Store.
• Metformin: an Old Therapy that Deserves a New Indication for the Treatment of Obesity - Curr Atheroscler Rep. 2016 Apr;18(4):16 - "Metformin is not currently used for weight loss or diabetes prevention because it lacks an FDA indication for obesity and/or pre-diabetes treatment. Based on the evidence, metformin has been shown to decrease the incidence of type 2 diabetes, and compares favorably to other weight-loss medications in terms of efficacy as well as safety. Thus, metformin should be considered for a treatment indication in patients with these conditions"
• SIRT3-AMPK Activation by Nitrite and Metformin Improves Hyperglycemia and Normalizes Pulmonary Hypertension Associated with Heart Failure with Preserved Ejection Fraction (PH-HFpEF) - Circulation. 2016 Jan 26 - "These studies validate a rodent model of metabolic syndrome and PH-HFpEF, suggesting a potential role of nitrite and metformin as a preventative treatment for this disease"
• Association between Metformin Use and Mortality after Cervical Cancer in Older Women with Diabetes - Cancer Epidemiol Biomarkers Prev. 2015 Dec 31 - "Cumulative dose of metformin after cervical cancer diagnosis was independently associated with a decreased risk of cervical cancer-specific mortality and overall mortality in a dose-dependent fashion (HR 0.79 ... This finding has important implications if validated prospectively, as metformin is inexpensive and can be easily combined with standard treatment for cervical cancer"
• Metformin and prostate cancer mortality: a meta-analysis - Cancer Causes Control. 2015 Nov 4 - "Metformin use was associated with improved overall survival in studies with clear risk window definition (HR 0.88, 95 % CI 0.86-0.90, p < 0.001) and in studies with potential immortal time bias (HR 0.52, 95 % CI 0.41-0.65, p < 0.001). No significant association with prostate cancer-specific mortality was detected (HR 0.76, 95 % CI 0.44-1.31, p = 0.33). Metformin use was associated with a decreased risk of biochemical recurrence (HR 0.79"
• Metformin use and risk of colorectal adenoma after polypectomy in patients with type 2 diabetes mellitus - Cancer Epidemiol Biomarkers Prev. 2015 Sep 16 - "Compared to patients not receiving diabetes medications (n=1,578), metformin-only use (n=457) was associated with lower adenoma recurrence risk (adjusted hazard ratio (HR)=0.76"
• Synergistic effects of metformin in combination with EGFR-TKI in treatment of patients with advanced non-small cell lung cancer and type 2 diabetes - Cancer Lett. 2015 Sep 1 - "epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment ... Metformin use is associated with improved survival and delayed onset of acquired resistance to EGFR-TKI"
• Effect of metformin on breast ductal carcinoma in situ proliferation in a randomized pre-surgical trial - Cancer Prev Res (Phila). 2015 Aug 14 - "Metformin is associated with lower breast cancer (BCa) risk in epidemiological studies and showed decreased proliferation in HER2-positive BCa in a pre-surgical trial ... We randomly assigned 200 non-diabetic patients diagnosed with invasive BCa in core biopsies to metformin, 1700 mg or placebo once daily for 28 days prior to surgery ... In tissue samples obtained following 4 weeks of study drug, proliferation was lower in HER2-positive DCIS for women randomized to metformin vs. placebo"
• Treatment With Metformin Improves Erectile Dysfunction in a Murine Model of Obesity Associated With Insulin Resistance - Urology. 2015 Jul 18 - "Treatment with metformin restored the erectile function in obese mice, through improvement of in vitro endothelial and nitrergic cavernosal relaxations. Therefore, use of metformin may be a good pharmacologic approach to treat insulin resistance-associated erectile dysfunction"
• Metformin inhibits age-related centrosome amplification in Drosophila midgut stem cells through AKT/TOR pathway - Mech Ageing Dev. 2015 May 16 - "Age-related changes in tissue-resident stem cells may be closely associated with tissue aging and age-related diseases, such as cancer. Centrosome amplification is a hallmark of cancers ... metformin, a recognized anti-cancer drug, inhibits age- and oxidative stress-induced centrosome amplification in ISCs ... Our study reveals the beneficial and protective effects of metformin on centrosome amplification via AKT/TOR signalling modulation"
• Metformin improves putative longevity effectors in peripheral mononuclear cells from subjects with prediabetes. A randomized controlled trial - Nutr Metab Cardiovasc Dis. 2015 Mar 24 - "Compared to baseline, metformin significantly improved metabolic parameters and insulin sensitivity, increased SIRT1 gene/protein expression and SIRT1 promoter chromatin accessibility, elevated mTOR gene expression with concomitant reduction in p70S6K phosphorylation in subjects' PBMCs, and modified the plasma N-glycan profile. Compared to placebo, metformin increased SIRT1 protein expression and reduced p70S6K phosphorylation (a proxy of mTOR activity). Plasma N-glycans were also favourably modified by metformin compared to placebo"
• Metformin inhibits the proliferation of human prostate cancer PC-3 cells via the downregulation of insulin-like growth factor 1 receptor - Biochem Biophys Res Commun. 2015 Apr 7 - "Recent studies have shown that metformin inhibits cancer cell proliferation and tumor growth both in vitro and in vivo ... Our results suggest that metformin is a potent inhibitor of the IGF-1/IGF-1R system and may be beneficial in prostate cancer treatment"
• Leucine amplifies the effects of metformin on insulin sensitivity and glycemic control in diet-induced obese mice - Metabolism. 2015 Mar 19 - "These data demonstrate that adding Leu to Met enables a dose reduction of 66% with improved efficacy and of 83% with comparable efficacy to standard metformin in diet-induced obese mice" - See leucine products at Amazon.com.
• Impacts of metformin and aspirin on life history features and longevity of crickets: trade-offs versus cost-free life extension? - Age (Dordr). 2015 Apr;37(2):9769 - "Both drugs significantly increased survivorship and maximal life span. Maximal longevity was 136 days for controls, 188 days (138 % of controls) for metformin, and 194 days (143 % of controls) for aspirin. Metformin and aspirin in combination extended longevity to a lesser degree (163 days, 120 % of controls)"
• Metformin reduces ovarian cancer risk in Taiwanese women with type 2 diabetes mellitus - Diabetes Metab Res Rev. 2015 Mar 28 - "The overall fully adjusted hazard ratio (95% confidence intervals) for ever- versus never-users was 0.658 (0.593-0.730). The fully adjusted hazard ratios for the first, second, and third tertiles of cumulative duration of metformin therapy were 1.169 (1.019-1.341), 0.761 (0.644-0.898) and 0.276 (0.225-0.340), respectively (P-trend <0.01); and 1.220 (1.067-1.395), 0.610 (0.513-0.725) and 0.305 (0.248-0.374), respectively (P-trend <0.01), for cumulative dose of metformin"
• Immune-mediated antitumor effect by type 2 diabetes drug, metformin - Proc Natl Acad Sci U S A. 2015 Jan 26 - "Metformin, a prescribed drug for type 2 diabetes, has been reported to have anti-cancer effects; however, the underlying mechanism is poorly understood. Here we show that this mechanism may be immune-mediated. Metformin enabled normal but not T-cell-deficient SCID mice to reject solid tumors. In addition, it increased the number of CD8+ tumor-infiltrating lymphocytes (TILs) and protected them from apoptosis and exhaustion characterized by decreased production of IL-2, TNFα, and IFNγ. CD8+ TILs capable of producing multiple cytokines were mainly PD-1-Tim-3+, an effector memory subset responsible for tumor rejection"
• Effects of Metformin on Energy Intake and Satiety in Obese Children - Diabetes Obes Metab. 2014 Dec 8 - "Compared with placebo, metformin treatment elicited significant reductions from baseline in adjusted mean energy intake after the pre-meal load (metformin: -104.7 ± 83.8 kcal vs. placebo: +144.2 ± 96.9 kcal; p = 0.034) independent of changes in body composition. Metformin also significantly decreased ratings of hunger (-1.5 ± 5.6 vs. +18.6 ± 6.3; p = 0.013) and increased ratings of fullness (+10.1 ± 6.2 vs. -12.8 ± 7.0; p = 0.01) following the pre-meal load"
• Combined use of vitamin D3 and metformin exhibits synergistic chemopreventive effects on colorectal neoplasia in rats and mice - Cancer Prev Res (Phila). 2014 Nov 21 - "These findings show that combined use of vitamin D3 and metformin exhibits synergistic effects against the development of early colon neoplasia. They suggest that the combined use of vitamin D3 and metformin may represent a novel strategy for chemoprevention of colorectal cancer" - See metformin at The Antiaging Store and vitamin D at Amazon.com.
• Effect of metformin therapy and dietary supplements on semen parameters in hyperinsulinaemic males - Andrologia. 2014 Oct 30 - "Nineteen hyperinsulinaemic male patients were treated for 3 months with metformin alone (Group A), and fifteen patients used metformin in combination with the nutritional supplement (Group B) ... The improvement in sperm morphology after treatment was similar for the two respective groups (P < 0.05). The morphological normal sperm forms increased from the mean percentage of 3.9 to 5.5% and from 4.2 to 5.5% for Group A and B respectively. Where a combination of metformin and the supplement were used (Group B), the combination treatment proved to be superior in obtaining enhanced chromatin packaging quality although not statistically significant (P = 0.5929) when compared with the metformin (Group A) group. The chromatin packaging quality in Group B improved with 10% while the improvement in Group A was approximately 8.3%"
• Antidiabetic drug metformin is effective on the metabolism of asymmetric dimethylarginine in experimental liver injury - Diabetes Res Clin Pract. 2014 Sep 16 - "Our findings showed that metformin administration for one week has a potency to protect liver through regulating ADMA metabolism in LPS/d-GalN-induced injury"
• SMILE upregulated by metformin inhibits the function of androgen receptor in prostate cancer cells - Cancer Lett. 2014 Sep 5 - "Metformin, a diabetes drug, has been reported to inhibit the growth of prostate cancer cells ... metformin upregulated the protein level of small heterodimer partner-interacting leucine zipper (SMILE), a coregulator of nuclear receptors, and knockdown of SMILE expression with shRNA abolished the inhibitory effect of metformin on AR function ... these results suggest that SMILE, which is induced by metformin, functions as a novel AR corepressor and may mediate the inhibitory effect of metformin on androgen-dependent growth of prostate cancer cells"
• Metformin Inhibits Epithelial-Mesenchymal Transition in Prostate Cancer Cells: Involvement of the Tumor Suppressor miR30a and its Target Gene SOX4 - Biochem Biophys Res Commun. 2014 Sep 5 - "Tumor metastasis is the leading cause of mortality and morbidity of prostate cancer (PCa) patients. Epithelial-mesenchymal transition (EMT) plays a critical role in cancer progression and metastasis. Recent evidence suggested that diabetic patients treated with metformin have lower PCa risk and better prognosis ... metformin significantly inhibits proliferation of Vcap and PC-3 cells, induces G0/G1 cell cycle arrest and inhibits invasiveness and motility capacity of Vcap cells"
• Metformin is associated with reduced risk of pancreatic cancer in patients with type 2 diabetes mellitus: A systematic review and meta-analysis - Diabetes Res Clin Pract. 2014 Apr 18 - "Use of metformin was associated with a significant lower risk of pancreatic cancer [RR 0.63"
• The prognostic value of metformin for cancer patients with concurrent diabetes- a systematic review and meta-analysis - Diabetes Obes Metab. 2014 Jan 27 - "A literature search was performed using the PubMed, EMbase and SciVerse Scopus databases ... metformin was associated with lower risk of all-cause mortality in cancer patients with concurrent diabetes, particularly for breast (pooled relative risk (RR) 0.70, 95% CI 0.55, 0.88; P=0.003), colorectal (RR 0.70, 95% CI 0.59, 0.84; P<0.001), ovarian (RR 0.44, 95% CI 0.30, 0.64; P<0.001) and endometrial cancer (RR 0.49, 95% CI 0.32, 0.73; P=0.001). In addition, metformin was associated with lower risks of cancer-specific mortality"
• Metformin: a metabolic disruptor and anti-diabetic drug to target human leukemia - Cancer Lett. 2014 Jan 21 - "We present here how metformin, an anti-diabetic drug that has attracted a strong interest for its recently discovered anti-cancer properties, can be envisioned as a new adjuvant approach to treat leukemia. Metformin may have a double-edged sword effect i) by acting on the organism to decrease hyperglycaemia and hyperinsulinemia in diabetic patients and ii) at the cellular level, by inhibiting the mTORC1-cancer supporting pathway through AMPK-dependent and independent mechanisms"
• Metformin Protects Against Systolic Overload-Induced Heart Failure Independent of AMP-Activated Protein Kinase α2 - Hypertension. 2014 Jan 13 - "metformin protects against adverse remodeling through a pathway that seems independent of AMPKα2"
• The relationship between metformin therapy and sleep quantity and quality in patients with Type 2 diabetes referred for potential sleep disorders - Diabet Med. 2013 Nov 16 - "Given that sleep disorders are known to be related to insulin resistance, and metformin has favourable effects on insulin resistance and on ventilatory drive, we sought to determine whether metformin therapy was related to sleep variables in a group of patients with Type 2 diabetes ... Total sleep time and sleep efficiency were higher in metformin-treated patients than in patients not treated with metformin [total sleep time: 6 h 39 min vs. 6 h 3 min, respectively (P = 0.002); sleep efficiency: 77.9 +/- 12.3 vs. 71.5 +/- 17.2%, respectively"
• Metformin Inhibits Skin Tumor Promotion in Overweight and Obese Mice - Cancer Prev Res (Phila). 2013 Nov 6 - "Collectively, the current data demonstrate that metformin given in the drinking water effectively inhibited skin tumor promotion in both overweight and obese mice"
• Anti-Diabetic Medications and the Risk of Colorectal Cancer in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis - Cancer Epidemiol Biomarkers Prev. 2013 Sep 16 - "Meta-analysis of observational studies showed an 11% reduction in CRC risk associated with metformin use (n=9 studies; OR, 0.89; 95% CI, 0.81-0.99), whereas TZD use was not associated with CRC risk (n=5 studies; OR, 0.96; 95% CI, 0.87-1.05). Conversely, a trend towards higher CRC risk was observed with sulfonylurea (n=7 studies; OR, 1.11; 95% CI, 0.97-1.26) and insulin (n=9 studies; OR, 1.33; 95% CI, 0.91-1.94) use, although these associations were not statistically significant"
• Relationship between metformin use, vitamin B12 deficiency, hyperhomocysteinemia and vascular complications in patients with type 2 diabetes - Endocr J. 2013 Sep 8 - "Metformin-induced B12 lowering in diabetes was associated with elevation of homocysteine, and hyperhomocysteinemia was independently related to retinopathy" - See vitamin B12 at Amazon.com.
• Increased Risk of Cognitive Impairment in Patients With Diabetes Is Associated With Metformin - Diabetes Care. 2013 Sep 5 - "Metformin use was associated with impaired cognitive performance. Vitamin B12 and calcium supplements may alleviate metformin-induced vitamin B12 deficiency and were associated with better cognitive outcomes" - See vitamin B12 at Amazon.com.
• Effects of Metformin Dose on Cancer Risk Reduction in Patients with Type 2 Diabetes Mellitus: A 6-Year Follow-up Study - Pharmacotherapy. 2013 Jul 17 - "Longitudinal Health Insurance Database ... A total of 65,754 age- and gender-matched patients without diabetes and no previous cancer diagnosis were extracted from the database ... Our results revealed dose-dependent effects of metformin on cancer risk and cancer onset times. A significant decrease in cancer risk was found in the monotherapy group who received more than 360 defined daily doses (DDDs) of metformin (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.24-0.66). The greatest decrease in cancer risk was observed in patients who took more than 1080 DDDs (HR 0.27, 95% CI 0.09-0.84). Significantly greater dose-dependent effects were seen in patients who used metformin in combination with other antidiabetic drugs" - See metformin at The Antiaging Store.
• Association Between Metformin Use and Risk of Prostate Cancer and Its Grade - J Natl Cancer Inst. 2013 Jul 13 - "There was no association between metformin use and risk of any prostate cancer (aOR = 1.03, 95% confidence interval [CI] = 0.96 to 1.1), high-grade cancer (aOR = 1.13, 95% CI = 0.96 to 1.32), low-grade cancer (aOR = 0.94, 95% CI = 0.82 to 1.06), or biopsy-diagnosed cancer (aOR = 0.98, 95% CI = 0.84 to 1.02)"
• Metformin for Weight Loss and Metabolic Control in Overweight Outpatients With Schizophrenia and Schizoaffective Disorder - Am J Psychiatry. 2013 Jul 12 - "Metformin was titrated up to 1,000 mg twice daily, as tolerated ... Mean change in body weight was -3.0 kg (95% CI=-4.0 to -2.0) for the metformin group and -1.0 kg (95% CI=-2.0 to 0.0) for the placebo group, with a between-group difference of -2.0 kg (95% CI=-3.4 to -0.6). Metformin also demonstrated a significant between-group advantage for BMI (-0.7; 95% CI=-1.1 to -0.2), triglyceride level (-20.2 mg/dL; 95% CI=-39.2 to -1.3), and hemoglobin A1c level (-0.07%; 95% CI=-0.14 to -0.004). Metformin-associated side effects were mostly gastrointestinal and generally transient, and they rarely led to treatment discontinuation" - Note: 3 kg is 6.6 pounds.
• A cohort study of metformin exposure and survival in patients with stage I-III colorectal cancer - Cancer Epidemiol Biomarkers Prev. 2013 Jun 10 - "Adult stage I-III colorectal cancer patients diagnosed 2001-2006 were identified from the National Cancer Registry Ireland. Use of metformin and other anti-diabetic medications was determined from a linked national prescription claims database ... High intensity exclusive metformin use was associated with a significant reduction in colorectal cancer-specific mortality (HR 0.44"
• Treatment with Metformin is Associated with Higher Remission Rate in Diabetic Patients with Thyroid Cancer - J Clin Endocrinol Metab. 2013 May 24 - "complete response (CR) ... progression free survival (PFS) ... Tumor size is smaller in patients treated with metformin suggesting inhibition of tumor growth by the drug. Among diabetics, absence of metformin therapy is an independent factor for decreased likelihood of CR and increased risk of shorter PFS"
• Insulin sensitizers and Serum Testosterone in men - Clin Endocrinol (Oxf). 2013 Apr 9 - "The effect of insulin resistance on the hypothalamo-pituitary-gonadal axis is sexually dimorphic1 . In women, it is associated with increased androgen production2 and, in men, usually with hypogonadism3 . Treatment with insulin sensitizers like metformin and pioglitazone in women lead to a decrease in serum total testosterone, while in men with T2DM, metformin therapy has been shown to decrease serum total testosterone4 . However, no data are available regarding the effect of pioglitazone on androgen profile in men"
• Metformin and Sulfonylureas in Relation to Cancer Risk in Type II Diabetes Patients: A Meta-analysis using primary data of published studies - Metabolism. 2013 Feb 15 - "This analysis using pooled primary data demonstrates that metformin use reduces, while sulfonylurea use may be associated with an increased cancer risk in subjects with T2DM"
• Effect of Pioglitazone Versus Metformin on Cardiovascular Risk Markers in Type 2 Diabetes - Adv Ther. 2013 Jan 22 - "The primary objective of this study was to evaluate the effect on C-reactive protein (CRP) after a 16-week treatment period with either pioglitazone or metformin ... Pioglitazone treated patients were found to have statistically significantly larger decreases in mean CRP levels (-0.4 mg/dL) compared to those treated with metformin (-0.2 mg/dL) (P = 0.04), as well as greater reductions in levels of mean fasting plasma glucose (-27 vs. -9 mg/dL; P = 0.01), serum insulin (-2 vs. -1.9 mU/L; P = 0.014), homeostatic model assessment (HOMA) (-1.2 vs. -0.9; P = 0.015), and E-selectin (-12.4 vs. +3.4 μg/mL; P = 0.01). Mean glycated hemoglobin (HbA(1c)) levels decreased in both treatment groups from baseline to week 16 (-0.4% in the pioglitazone group, -0.2% in the metformin group; P = 0.36). Pioglitazone treatment was also found to be associated with a statistically significant increase in total cholesterol levels (+10 mg/dL in the pioglitazone arm, -3 mg/dL in the metformin arm; P = 0.05) and a decrease in liver enzyme levels"
• Metformin and Prostate Cancer: Reduced Development of Castration-resistant Disease and Prostate Cancer Mortality - Eur Urol. 2012 Dec 14 - "castration-resistant prostate cancer (CRPC) ... prostate-specific antigen-recurrence-free survival (PSA-RFS), distant metastases-free survival (DMFS), prostate cancer-specific mortality (PCSM), overall survival (OS) ... With a median follow-up of 8.7 yr, the 10-yr actuarial rates for metformin, diabetic non-metformin, and nondiabetic patients for PCSM were 2.7%, 21.9%, and 8.2% (log-rank p ≤ 0.001), respectively. Metformin use independently predicted (correcting for PSA, T stage, Gleason score, age, diabetic status, and androgen-deprivation therapy use) improvement in all outcomes compared with the diabetic non-metformin group; PSA-RFS (hazard ratio [HR]: 1.99 [1.24-3.18]; p=0.004), DMFS (adjusted HR: 3.68 [1.78-7.62]; p<0.001), and PCSM (HR: 5.15 [1.53-17.35]; p=0.008). Metformin use was also independently associated with a decrease in the development of CRPC in patients experiencing biochemical failure compared with diabetic non-metformin patients (odds ratio: 14.81 [1.83-119.89]; p=0.01)"
• Initial Metformin or Sulfonylurea Exposure and Cancer Occurrence among Patients with Type 2 Diabetes Mellitus - Diabetes Obes Metab. 2012 Nov 8 - "The age standardized incidences of cancer were 7.5 and 8.5 per 1000 person-years for the metformin and sulfonylurea exposure groups, respectively ... This study provides evidence that cancer incidence in the first few years after starting metformin or sulfonylurea therapy in type 2 diabetes patients is not much affected by choice of hypoglycemic drug class" - Note:  It doesn't seem like they can justify that conclusion.  1 / 7.5 = 13.3% reduced risk with metformin over sulfonylurea therapy.
• Metformin and reduced risk of hepatocellular carcinoma in diabetic patients: a meta-analysis - Scand J Gastroenterol. 2012 Nov 9 - "Medline and Embase databases were searched to identify the relevant studies between January 1966 and December 2011 ... the overall prevalence of HCC was 3.40% (562/16,549) in DM patients. The overall analysis showed a significantly reduced risk of HCC in metformin users versus nonusers in diabetic patients (relative risk (RR) 0.24, 95% confidence interval (CI) 0.13-0.46, p < 0.001)"
• Risk factors for intrahepatic cholangiocarcinoma: Association between metformin use and reduced cancer risk - Hepatology. 2012 Oct 11 - "Metformin is purportedly associated with a reduced risk for various cancers ... treatment with metformin was significantly associated with a 60% reduction in ICC risk in diabetic patients" - Note:  The point is that it's one more to the list of cancers reduced by metformin.
  • Cholangiocarcinoma - Wikipedia, the free encyclopedia - "Cholangiocarcinoma is a medical term denoting a form of cancer that is composed of mutated epithelial cells (or cells showing characteristics of epithelial differentiation) that originate in the bile ducts which drain bile from the liver into the small intestine. Other biliary tract cancers include pancreatic cancer, gallbladder cancer, and cancer of the ampulla of Vater"
• Lymphocyte-suppressing and systemic anti-inflammatory effects of high-dose metformin in simvastatin-treated patients with impaired fasting glucose - Atherosclerosis. 2012 Oct 12 - "Metformin, but not placebo, administered to simvastatin-treated IFG subjects reduced plasma levels of C-reactive protein, soluble intercellular adhesion molecule-1, as well as lymphocyte release of interleukin-2, interferon-γ and tumor necrosis factor-α, which was accompanied by the improvement in insulin sensitivity and a reduction in free fatty acid levels ... The obtained results indicate that metformin potentiates lymphocyte-suppressing and systemic anti-inflammatory effects of simvastatin in subjects with IFG. These effects of statin-metformin combination therapy may play a role in the prevention and treatment of atherosclerosis and its complications in patients with early glucose metabolism abnormalities"
• What Next after Metformin? A Retrospective Evaluation of the Outcome of Second-Line, Glucose-Lowering Therapies in People with Type 2 Diabetes - J Clin Endocrinol Metab. 2012 Oct 17 - "Sulfonylurea monotherapy had significantly higher hazard ratios (HRs) for all-cause mortality (HR 1.459, 1.207-1.763); MACE (HR 1.578, 1.187-2.099); stroke (HR 1.444, 1.050-1.987); and the combined end point (HR 1.381, 1.194-1.597). Metformin plus pioglitazone had significantly lower adjusted HRs for all-cause mortality (HR 0.707, 0.515-0.970) and the combined end point (HR 0.747, 0.612-0.911)"
• Effects of metformin on markers of oxidative stress and antioxidant reserve in patients with newly diagnosed type 2 diabetes: A randomized clinical trial - Clin Nutr. 2012 Aug 21 - "Baseline values of the oxidative stress markers did not differ significantly between the two groups. In cases, after three months treatment, there was a significant reduction in AOPP [Advanced Oxidation Protein Products] (137.52 +/- 25.59, 118.45 +/- 38.42, p < 0.001), and AGE [advanced glycation end-products] (69.28 +/- 4.58, 64.31 +/- 8.64, p = 0.002) ... Use of metformin is more effective in reducing oxidative stress compared with lifestyle modification alone"
• Diabetes, metformin use, and colon cancer: A population-based cohort study in Taiwan - Eur J Endocrinol. 2012 Jul 9 - "Even though diabetes patients had a significantly higher probability of receiving examinations that could lead to the detection of colon cancer, they had a significantly higher risk (24%) of this cancer after adjustment. Metformin users had a significantly lower risk (27%) of colon cancer. While comparing patients with diabetes for <1, 1-3, and ≥3 years to non-diabetes individuals, the adjusted relative risk (95% confidence interval) was 1.308 (1.020-1.679), 1.087 (0.900-1.313), and 1.185 (1.055-1.330), respectively. The higher risk among those with diabetes for <1 year suggested a possible reverse causality or a link with prediabetes. However, diabetes still might play some role in colon cancer development among those with diabetes for ≥3 years. The duration of metformin use showed an inverse trend, with a significant relative risk of 0.643 (0.490-0.845) in users for ≥3 years, when compared to non-users. In addition, metformin may reduce colon cancer risk associated with chronic obstructive pulmonary disease (a surrogate for smoking)"
• Metformin for Treatment of Antipsychotic-Induced Amenorrhea and Weight Gain in Women With First-Episode Schizophrenia: A Double-Blind, Randomized, Placebo-Controlled Study - Am J Psychiatry. 2012 Jun 15 - "A total of 76 patients completed the 6-month trial. Significantly more patients in the metformin group (N=28, 66.7%) than in placebo group (N=2, 4.8%) resumed their menstruation. Among patients treated with metformin, BMI decreased by a mean of 0.93 and the insulin resistance index by 2.04. In contrast, patients who received placebo had a mean increase in BMI of 0.85. The prolactin, LH, and testosterone levels and LH/FSH ratio decreased significantly in the metformin group at months 2, 4, and 6, but these levels did not change in the placebo group ... Metformin was effective in reversing antipsychotic-induced adverse events, including restoration of menstruation, promotion of weight loss, and improvement in insulin resistance in female patients with schizophrenia"
• Diabetes, Metformin, and Breast Cancer in Postmenopausal Women - J Clin Oncol. 2012 Jun 11 - "assessed associations among diabetes, metformin use, and breast cancer in postmenopausal women participating in Women's Health Initiative clinical trials ... observed over a mean of 11.8 years ... Women with diabetes receiving medications other than metformin had a slightly higher incidence of breast cancer (hazard ratio [HR], 1.16; 95% CI, 0.93 to 1.45), and women with diabetes who were given metformin had lower breast cancer incidence (HR, 0.75; 95% CI, 0.57 to 0.99). The association was observed for cancers positive for both estrogen receptor and progesterone receptor and those that were negative for human epidermal growth factor receptor 2 ... Metformin use in postmenopausal women with diabetes was associated with lower incidence of invasive breast cancer"
• Metformin for Liver Cancer Prevention in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis - J Clin Endocrinol Metab. 2012 Apr 20 - "In meta-analyses, metformin was associated with an estimated 62% reduction in the risk of liver cancer among patients with type 2 diabetes ... When restricting the analysis to the four studies related to hepatocellular carcinoma, metformin was again associated with a significantly lower cancer risk (odds ratio 0.30, 95% confidence interval 0.17, 0.52; P < 0.001), and there was evidence of significant heterogeneity between these four studies"
• Insulin resistance: A significant risk factor of endometrial cancer - Gynecol Oncol. 2012 Mar 23 - "Risk factors of insulin resistance, such as the inflammatory mediators, adipokines adiponectin, leptin and plasminogen activator inhibitor-1 and excessive androgen are also risk factors of endometrial cancer. High levels of insulin induced by insulin resistance have been found to exert direct and indirect effects that contribute to the development of endometrial cancer. Insulin directly promotes cell proliferation and survival through the PI3K/Akt and Ras/MAPK pathways. Moreover, the network among insulin, estrogen and insulin-like growth factor-1 also contributes to the development of endometrial cancer. Indirectly, insulin leads to changes in sex hormone levels, including increases in the levels of estrogen. Additionally, a small number of studies suggested that metformin, an insulin-sensitizing agent, has therapeutic potential for endometrial cancer"
• Metformin-based treatment for obesity-related hypertension: a randomized, double-blind, placebo-controlled trial - J Hypertens. 2012 Apr 19 - "metformin (500 mg once per day) or placebo ... At 24 weeks, metformin compared with placebo did not have significant effects on blood pressure, blood glucose, high-density or low-density lipoprotein cholesterol, but it did reduce total serum cholesterol (0.27mmol/l, P = 0.038). Metformin also significantly reduced weight (-0.7 kg, P = 0.006), BMI (-0.2 kg/m, P = 0.024), waist circumference (-0.9 cm, P =���0.008), and both subcutaneous (-6.1 cm, P = 0.043) and visceral adiposity (-5.4 cm, P = 0.028) as measured by computed tomography, and lowered serum high-sensitivity C-reactive protein levels (-0.6 mg/dl, P < 0.001). There was no significant difference in adverse events"
• Statin Use As a Moderator of Metformin Effect on Risk for Prostate Cancer Among Type 2 Diabetic Patients - Diabetes Care. 2012 Mar 28 - "Mean follow-up was ~5 years, and 7.5% had a PCa diagnosis. Statin use modified the effect of metformin on PCa incidence (P < 0.0001). Metformin was associated with a significantly reduced PCa incidence among patients on statins (HR 0.69 [95% CI 0.50-0.92]; 17 cases/533 metformin users vs. 135 cases/2,404 sulfonylureas users) and an increased PCa incidence among patients not on statins (HR 2.15 [1.83-2.52]; 22 cases/175 metformin users vs. 186 cases/1,930 sulfonylureas users). The HR of PCa incidence for those taking metformin and statins versus those taking neither medication was 0.32"
• Pioglitazone may accelerate disease course of slowly progressive type 1 diabetes - Diabetes Metab Res Rev. 2011 Nov;27(8):951-3 - "The enrolled SPIDDM patients were randomly allocated to a pioglitazone or metformin group. When the haemoglobin A1C level was more than 8% on two consecutive occasions, the case was considered to reach the end point ... By 4 years post-intervention, all patients had reached the end point in the pioglitazone group, whereas only 20% of patients had reached the end point in the metformin group"
• Reduced Risk of Colorectal Cancer With Metformin Therapy in Patients With Type 2 Diabetes: A meta-analysis - Diabetes Care. 2011 Oct;34(10):2323-8 - "Both in vitro and in vivo studies indicate that metformin inhibits cancer cell growth and reduces cancer risk ... The analysis included five studies comprising 108,161 patients with type 2 diabetes. Metformin treatment was associated with a significantly lower risk of colorectal neoplasm (relative risk [RR] 0.63 [95% CI 0.50-0.79]; P < 0.001). After exclusion of one study that investigated colorectal adenoma, the remaining four studies comprised 107,961 diabetic patients and 589 incident colorectal cancer cases during follow-up. Metformin treatment was associated with a significantly lower risk of colorectal cancer (0.63 [0.47-0.84]; P = 0.002)"
• The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus - Int J Cancer. 2011 Sep 12 - "Metformin use has been associated with decreased cancer risk and mortality ... We identified 595 patients who were diagnosed both CRC and diabetes mellitus. Patients were compared by two groups; 258 diabetic patients taking metformin and 337 diabetic patients not taking metformin ... After a median follow-up of 41 months, there were 71 total deaths (27.5%) and 55 CRC-specific deaths (21.3%) among 258 patients who used metformin, compared with 136 total deaths (40.4%) and 104 CRC-specific deaths (30.9%) among 337 patients who did not use metformin. Metformin use was associated with decreased overall mortality (P=0.018) and CRC-specific mortality (P=0.042) by univariate analysis. After adjustment for clinically relevant factors, metformin use showed lower risk of overall mortality (HR, 1.45; 95% CI, 1.084-1.934; P=0.016) and CRC-specific mortality (HR, 1.44; 95% CI, 1.026-2.061; P=0.035) in CRC patients with diabetes. Metformin use in CRC patients with diabetes is associated with lower risk of CRC-specific and overall mortality"
• Cancer mortality reduction and metformin. A retrospective cohort study in type 2 diabetic patients - Diabetes Obes Metab. 2011 Aug - "All-cause and cancer-related deaths occurred in: 9.2%, 1.6% of metformin users, 13.1%, 3.0% of sulfonylureas users and 26.8%, 4.8%of insulin users, respectively. In a Cox regression model for competing risks, adjusted for propensity score, metformin users showed a lower cancer mortality risk (HR=0.56;95%CI 0.34-0.94), while insulin was positively associated with other-than-cancer-mortality (HR=1.56; 1.22-1.99). Each 5-year metformin exposure was associated with a reduction in cancer death by 0.73, whereas every 5-year insulin exposure was associated with 1.25-fold increase in other-than-cancer death. Standardized mortality ratios for cancer and other-than-cancer mortality in metformin users were 43.6 (95%CI 25.8-69.0) and 99.1 (79.3-122.5) respectively, in comparison with the general population. Conclusions: Metformin users showed a lower risk of cancer-related mortality than not users or patients on diet only; this may represent another reason to choose metformin as a first-line therapy in T2DP"
• Effects of pioglitazone vs metformin on circulating endothelial microparticles and progenitor cells in patients with newly diagnosed type 2 diabetes - a randomized controlled trial - Diabetes Obes Metab. 2011 Jan 21 - "Participants assigned to pioglitazone gained more weight and experienced greater improvements in some coronary risk measures (HDL-cholesterol, triglycerides, adiponectin, and C-reactive protein) than did those assigned to metformin. Conclusion: Compared with metformin, pioglitazone treatment improved the imbalance between endothelial damage and repair capacity, and led to more favorable changes in coronary risk factors in patients with newly-diagnosed type 2 diabetes"
• Effects of Metformin on Body Weight and Body Composition in Obese Insulin-Resistant Children: A Randomized Clinical Trial - Diabetes. 2011 Jan 12 - "1,000 mg metformin (n = 53) or placebo (n = 47) twice daily for 6 months ...Children prescribed metformin had significantly greater decreases in BMI (difference -1.09 kg/m(2), CI -1.87 to -0.31, P = 0.006), body weight (difference -3.38 kg, CI -5.2 to -1.57, P < 0.001), BMI Z score (difference between metformin and placebo groups -0.07, CI -0.12 to -0.01, P = 0.02), and fat mass (difference -1.40 kg, CI -2.74 to -0.06, P = 0.04). Fasting plasma glucose (P = 0.007) and homeostasis model assessment (HOMA) insulin resistance index (P = 0.006) also improved more in metformin-treated children than in placebo-treated children. Gastrointestinal symptoms were significantly more prevalent in metformin-treated children, which limited maximal tolerated dosage in 17%. During the 6-month open-label phase, children treated previously with placebo decreased their BMI Z score; those treated continuously with metformin did not significantly change BMI Z score further. CONCLUSIONS Metformin had modest but favorable effects on body weight, body composition, and glucose homeostasis in obese insulin-resistant children participating in a low-intensity weight-reduction program" - Note: 3.38 kg equals 7.4 pounds.
• Metformin Treatment Exerts Antiinvasive and Antimetastatic Effects in Human Endometrial Carcinoma Cells - J Clin Endocrinol Metab. 2010 Dec 29 - "In vitro invasion in ECC-1 cells was significantly attenuated by sera from PCOS women after 6 months of metformin treatment (850 mg twice daily) compared to matched controls (P < 0.01). These effects appear to be associated with NF-κB, MMP-2/9, as well as Akt and Erk1/2 pathways that are known to be important regulators of inflammation, tumor invasion and metastasis. Conclusions: Metformin, potentially, may serve as adjuvant treatment in the management of patients with endometrial cancer"
• Metformin and incident breast cancer among diabetic women: a population-based case-control study in Denmark - Cancer Epidemiol Biomarkers Prev. 2010 Nov 30 - "Metformin users were less likely to be diagnosed with breast cancer (OR=0.77; 95% CI=0.61, 0.99) than non-metformin users. Adjusting for diabetes complications, clinically diagnosed obesity, and important predictors of breast cancer did not substantially alter the association (OR=0.81; 95%CI=0.63, 0.96). CONCLUSION: Our results suggest that metformin may protect against breast cancer in type 2 diabetic peri- or postmenopausal women. Impact: This study supports the growing evidence of a role for metformin in breast cancer chemoprevention"
• Effects of pioglitazone and metformin fixed-dose combination therapy on cardiovascular risk markers of inflammation and lipid profile compared with pioglitazone and metformin monotherapy in patients with type 2 diabetes - J Clin Hypertens (Greenwich). 2010 Dec;12(12):973-82 - "fixed-dose combination (FDC) of pioglitazone/metformin compared with the respective monotherapies ... FDC and pioglitazone increased high-density lipoprotein cholesterol by 14.20% and 9.88%, respectively, vs an increase of 6.09% with metformin (P<.05, metformin vs FDC). Triglycerides decreased with all three treatments -5.95%, -5.54% and -1.78%, respectively; P=not significant). FDC and pioglitazone significantly decreased small low-density lipoprotein and increased large low-density lipoprotein particle concentrations. Reductions in high-sensitivity C-reactive protein were greater in the FDC and pioglitazone groups. Increases in adiponectin were significant in the FDC and pioglitazone groups (P<.0001 vs metformin). Overall, adverse events were not higher with the FDC. Thus, treatment with the FDC resulted in improved levels of CV biomarkers, which were better than or equal to monotherapy"
• Metformin inhibits HMGB1 release in LPS-treated RAW 264.7 cells and increases survival rate of endotoxaemic mice - Br J Pharmacol. 2010 Nov 22 - "lipopolysaccharide (LPS)-treated animals and cells ... metformin significantly attenuates the pro-inflammatory response induced by LPS both in vivo and in vitro. Metformin improved survival in a mouse model of lethal endotoxaemia by inhibiting HMGB1 release. AMPK activation was implicated as one of the mechanisms contributing to this inhibition of HMGB1 secretion"
• Metformin Use and Mortality Among Patients With Diabetes and Atherothrombosis - Arch Intern Med. 2010 Nov 22;170(21):1892-1899 - "The mortality rates were 6.3% (95% confidence interval [CI], 5.2%-7.4%) with metformin and 9.8% 8.4%-11.2%) without metformin; the adjusted hazard ratio (HR) was 0.76 (0.65-0.89; P < .001). Association with lower mortality was consistent among subgroups, noticeably in patients with a history of congestive heart failure (HR, 0.69; 95% CI, 0.54-0.90; P = .006), patients older than 65 years (0.77; 0.62-0.95; P = .02), and patients with an estimated creatinine clearance of 30 to 60 mL/min/1.73 m(2) (0.64; 95% CI, 0.48-0.86; P = .003) (to convert creatinine clearance to mL/s/m(2), multiply by 0.0167)"
• Metformin treatment is associated with a low risk of mortality in diabetic patients with heart failure: a retrospective nationwide cohort study - Diabetologia. 2010 Sep 14 - "With sulfonylurea monotherapy used as the reference, adjusted hazard ratios for all-cause mortality associated with the different treatment groups were as follows: metformin 0.85 (95% CI 0.75-0.98, p = 0.02), metformin + sulfonylurea 0.89 (95% CI 0.82-0.96, p = 0.003), metformin + insulin 0.96 (95% CI 0.82-1.13, p = 0.6), metformin + insulin + sulfonylurea 0.94 (95% CI 0.77-1.15, p = 0.5), sulfonylurea + insulin 0.97 (95% CI 0.86-1.08, p = 0.5) and insulin 1.14 (95% CI 1.06-1.20, p = 0.0001)"
• Metformin is associated with improved left ventricular diastolic function measured by tissue Doppler imaging in patients with diabetes - Eur J Endocrinol. 2010 Aug 2 - "use of metformin was associated with a shorter IVRT (parameter estimate -9.9 ms, p=0.049), and higher e' (parameter estimate +0.52 cm/s, p=0.03), compared to no use of metformin. The effects of metformin were not altered by concomitant use of sulfonylureas or insulin (p for interactions >0.4). Conclusions: Use of metformin is associated with improved left ventricular relaxation, as compared with no use of metformin"
• Long-term metformin use is associated with decreased risk of breast cancer - Diabetes Care. 2010 Mar 18 - "The mean age was 67.5 (+/-std 10.5) years at the time of the cancer diagnosis. Long-term use of 40+ prescriptions (>5 years) of metformin, based on 17 exposed cases and 120 exposed controls, was associated with an adjusted OR of 0.44 (95% CI 0.24-0.82) for developing breast cancer, as compared to no use of metformin"
• Effects of metformin with or without supplementation with folate on homocysteine levels and vascular endothelium of women with polycystic ovary syndrome - Diabetes Care. 2009 Nov 23 - "Metformin exerts a slight but significant deleterious effect on serum Hcy levels in patients with PCOS, and supplementation with folate is useful to increase the beneficial effect of metformin on the vascular endothelium"
• Metformin associated with lower cancer mortality in type 2 diabetes (ZODIAC-16) - Diabetes Care. 2009 Nov 16 - "Median follow-up time was 9.6 years, average age at baseline was 68 years, and average HbA1c was 7.5%. Five hundred seventy patients died, of which 122 from malignancies. SMR for cancer mortality was 1.47 (95%CI 1.22-1.76). In patients taking metformin compared to patients not taking metformin at baseline, the adjusted hazard ratio (HR) for cancer mortality was 0.43 (95%CI 0.23-0.80), and the HR with every increase of 1 gram of metformin was 0.58 (95%CI 0.36-0.93) ... In general, patients with type 2 diabetes are at increased risk for cancer mortality. In our group, metformin use was associated with lower cancer mortality when compared to non-metformin use. Although the design cannot be conclusive about causality, our results suggest a protective effect of metformin on cancer mortality"
• Many Americans Have Prediabetes and Should Be Considered for Metformin Therapy - Diabetes Care. 2009 Oct 6 - "Criteria for consideration of metformin included the presence of both IFG and IGT, with >/=1 additional diabetes risk factor: age <60 years, BMI >/=35 kg/m(2), family history of diabetes, elevated triglycerides, reduced HDL-cholesterol, hypertension, or A1c >6.0% ... To the extent that our findings are representative of the U.S. population, approximately 1 in 12 adults has a combination of prediabetes and risk factors which may justify consideration of metformin treatment for diabetes prevention"
• Metformin use and prostate cancer in Caucasian men: results from a population-based case-control study - Cancer Causes Control. 2009 Aug 4 - "In Caucasian men, metformin use was more common in controls than in cases (4.7 vs. 2.8%, p = 0.04), resulting in a 44% risk reduction for PCa (adjusted OR = 0.56; 95% CI 0.32-1.00). No association was seen in African-American men"
• Effect of adjunct metformin treatment on levels of plasma lipids in patients with type 1 diabetes - Diabetes Obes Metab. 2009 Jun 25 - "After 1 year, in those patients who did not start or stop statin therapy during the trial, metformin treatment significantly reduced total and LDL cholesterol by approximately 0.3 mmol/l compared with placebo (p = 0.021 and p = 0.018 respectively). Adjustment for statin use or known cardiovascular disease did not change conclusions. In statin users (metformin: n = 22, placebo: n = 13), metformin significantly lowered levels of LDL and non-HDL cholesterol by approximately 0.5 mmol/l compared with placebo"
• New users of metformin are at low risk of incident cancer: A cohort study among people with type 2 diabetes - Diabetes Care. 2009 Jun 29 - "Activation of AMPK can suppress tumour formation and inhibit cell growth, in addition to lowering blood glucose levels. We tested the hypothesis that metformin reduces the risk of cancer in people with type 2 diabetes ... Cancer was diagnosed among 7.3% of 4,085 metformin users compared with 11.6% of 4,085 comparators, with median times to cancer of 3.5 years and 2.6 years respectively (p < 0.001). The unadjusted hazard ratio for cancer was 0.46 (0.40-0.53). After adjusting for sex, age, BMI, HbA1c, deprivation, smoking and other drug use, there was still a significantly reduced risk of cancer associated with metformin: 0.63 (0.53-0.75)"
• Metformin restores impaired HDL-mediated cholesterol efflux due to glycation - Atherosclerosis. 2009 Mar 19 - "In the presence of metformin or aminoguanidine (100mM), glycated HDL-mediated cholesterol efflux was restored to 97.5+/-4.3% and 96.9+/-3.1%, respectively"
• Pioglitazone Improves Cardiac Function and Alters Myocardial Substrate Metabolism Without Affecting Cardiac Triglyceride Accumulation and High-Energy Phosphate Metabolism in Patients With Well-Controlled Type 2 Diabetes Mellitus - Circulation. 2009 Apr 6 - "were assigned to pioglitazone (30 mg/d) or metformin (2000 mg/d) and matching placebo for 24 weeks ... No patient developed heart failure. Both therapies similarly improved glycemic control, whole-body insulin sensitivity, and blood pressure. Pioglitazone versus metformin improved the early peak flow rate (P=0.047) and left ventricular compliance. Pioglitazone versus metformin increased myocardial glucose uptake (P<0.001), but pioglitazone-related diastolic improvement was not associated with changes in myocardial substrate metabolism. Metformin did not affect myocardial function but decreased cardiac work relative to pioglitazone (P=0.006), a change that was paralleled by a reduced myocardial glucose uptake and fatty acid oxidation. Neither treatment affected cardiac high-energy phosphate metabolism or triglyceride content. Only pioglitazone reduced hepatic triglyceride content" - I still take pioglitazone even though I don't have diabetes because I feel that higher glucose levels are a major cause of aging.  There doesn't seem to be any evidence that it has the heart rises that rosiglitazone has.  See Pioglitazone at OffshoreRx1.com.
• Efficacy and safety of therapy with metformin plus pioglitazone in the treatment of patients with type 2 diabetes: a double-blind, placebo-controlled, clinical trial - Curr Med Res Opin. 2009 Mar 23 - "Mean HbA(1c) was reduced by 0.67% in patients receiving pioglitazone plus metformin versus an increase of 0.25% in those receiving metformin alone (p < 0.0001). After 8 weeks' treatment and until the end of the study, HbA(1c) was significantly lower with pioglitazone plus metformin and more patients in this group achieved an HbA(1c) < 6.5% (38.6% vs. 8.1%; p < 0.0001). FBG was also reduced by a significantly greater amount in patients receiving pioglitazone plus metformin compared with metformin monotherapy (-20.5 vs. 1.9 mg/dl; p < 0.0001). Combination therapy was associated with significantly increased HDL-cholesterol, total cholesterol, and adiponectin, and significantly decreased levels of fasting insulin, free fatty acids, and homeostasis model assessment insulin resistance (HOMA-R) compared with metformin monotherapy" - See pioglitazone at OffshoreRx1.com.
• Treatment of white coat hypertension with metformin - Int Heart J. 2008 Nov;49(6):671-9 - "White coat hypertension (WCH) is most likely a disorder associated with metabolic syndrome ... Twenty-five cases (14.7%) stopped metformin therapy due to excessive anorexia. At the end of a 6-month period, there were highly significant differences between the two groups with respect to the prevalences of resolved WCH, hyperbetalipoproteinemia, hypertriglyceridemia, dyslipidemia, overweight and obesity, and decreased fasting plasma glucose below 110 mg/dL ... Thus, the management of WCH should not focus solely on the regulation of blood pressure with antihypertensive medications, but rather on the prevention of future excess weight and various associated disorders, and metformin alone is an effective therapeutic option, most likely due to its powerful inhibitory effect on appetite"
• Effect of Metformin-Containing Antidiabetic Regimens on All-cause Mortality in Veterans With Type 2 Diabetes Mellitus - Am J Med Sci. 2008 Sep;336(3):241-7 - "Treatment of T2DM with regimens containing metformin alone or in combination with other hypoglycemic agents was associated with reduced all-cause mortality compared with regimens without metformin"
• The effects of 8 months of metformin on circulating GGT and ALT levels in obese women with polycystic ovarian syndrome - Int J Clin Pract. 2008 Jun 19 - "treated with metformin 1500 or 2550 mg/day for 8 months ... Mean weight, serum ALT and GGT decreased from 100.3 to 96.6 kg (p < 0.0001), 29.7 to 25.8 U/l (p = 0.012) and 21.4 to 16.9 U/l (p < 0.0001) respectively ... In women with baseline ALT > 29.7 U/l (median), ALT reduction was highly significant (p = 0.005); however in those with baseline ALT < 29.7 U/l, ALT did not change despite similar weight reduction. There was no difference in reductions in ALT and GGT when the two metformin doses were compared"
• Role of Metformin for Weight Management in Patients Without Type 2 Diabetes (June) - Ann Pharmacother. 2008 May 13 - "The weight loss effects of metformin in overweight or obese adults and adolescents without diabetes appear promising; however, trials have been limited by small patient populations and weak design. Metformin may also have a positive effect on metabolic parameters such as waist circumference, fasting insulin and glucose levels, and triglycerides" - See metformin at at OffshoreRx1.com.
• Metformin improves polycystic ovary syndrome symptoms irrespective of pre-treatment insulin resistance - Eur J Endocrinol. 2007 Nov;157(5):669-76 - "In the overweight and obese PCOS groups, metformin also showed the expected beneficial effects ... Metformin improves parameters of IR, hyperandrogenemia, anovulation, and acne in PCOS irrespective of pre-treatment IR or obesity"
• Decreased in vivo oxidative stress and decreased platelet activation following metformin treatment in newly diagnosed type 2 diabetic subjects - Diabetes Metab Res Rev. 2007 Oct 30 - "These data suggest that metformin could improve oxidative stress, preserve antioxidant function and restrain platelet activation in type 2 diabetes"
• Liver dysfunction in paediatric obesity: a randomized, controlled trial of metformin - Acta Paediatr. 2007 Sep;96(9):1326-32 - "In obese adolescents fed ad libitum, metformin (a) prevented the rise in ALT concentrations that were observed in placebo-treated subjects at the 3 to 5 month time-points (p < 0.05); (b) reduced (p < 0.01) the percentage of all ALT values exceeding 40 U/L; and (c) caused a modest (10%) but statistically significant (p < 0.05) reduction in serum ALT in Caucasian subjects. Metformin had no effect on ALT levels or the ALT to AST ratio in the five African American adolescents enrolled in the study ... metformin might reduce the rates or severity of liver dysfunction in selected high-risk adolescents"
• Metformin as an adjunctive treatment to control body weight and metabolic dysfunction during olanzapine administration: A multicentric, double-blind, placebo-controlled trial - Schizophr Res. 2007 Jul;93(1-3):99-108 - "Metformin may safely assist olanzapine-treated patients in body weight and carbohydrate metabolism control"
• Comparison of the effects of pioglitazone and metformin on insulin resistance and hormonal markers in patients with impaired glucose tolerance and early diabetes - Hypertens Res. 2007 Jan;30(1):23-30 - "pioglitazone was superior to metformin for the improvement of insulin resistance and adiponectin ... Early intervention with pioglitazone or metformin therapy may reduce the incidence of future cardiovascular disease in subjects with impaired glucose tolerance or early diabetes"
• Treating the metabolic syndrome - Expert Rev Cardiovasc Ther. 2007 May;5(3):491-506 - "appropriate treatment of MS components often requires pharmacologic intervention with insulin-sensitizing agents, such as metformin and thiazolidinediones, while statins and fibrates, or angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are the first-line lipid-modifying or antihypertensive drugs"
• Rosiglitazone is more effective than metformin in improving fasting indexes of glucose metabolism in severely obese, non-diabetic patients - Diabetes Obes Metab. 2007 Mar 29 - "Our study shows that in severely obese, non-diabetic, hyperinsulinaemic patients undergoing a nutritional programme, rosiglitazone is more effective than metformin in producing favourable changes in fasting-based indexes of glucose metabolism, with a reduction of both insulin resistance and hyperinsulinaemia. In spite of previous studies reporting rosiglitazone-induced body weight gain, in our study the joint treatment with diet and rosiglitazone was accompanied by weight loss and fat mass reduction"
• Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B(12) in patients with type 2 diabetes mellitus - J Diabetes Complications. 2007 Mar-Apr;21(2):118-23 - "In patients with type 2 diabetes, metformin reduces levels of folate and vitamin B(12) and increases Hcy. Conversely, rosiglitazone decreases Hcy levels in this time period"
• A randomized trial of the effects of rosiglitazone and metformin on inflammation and subclinical atherosclerosis in patients with type 2 diabetes - Am Heart J. 2007 Mar;153(3):445.e1-6 - "Metformin and rosiglitazone treatment led to similar significant improvements in glycemic control (HbA(1c) -1.08% in the rosiglitazone group and -1.18% in the metformin group, P = nonsignificant). High-sensitivity C-reactive protein levels decreased by an average of 68% in the rosiglitazone group (5.99 +/- 0.88 to 1.91 +/- 0.28 mg/L, P < .001), compared with a nonsignificant 4% reduction in hsCRP with metformin"
• Effects of rosiglitazone and metformin on inflammatory markers and adipokines: decrease in interleukin-18 is an independent factor for the improvement of homeostasis model assessment-beta in type 2 diabetes mellitus - Clin Endocrinol (Oxf). 2007 Feb;66(2):282-9 - "Rosiglitazone, but not metformin, improved the plasma concentrations of inflammatory markers and adipokines in patients with type 2 diabetes mellitus"
• Glycemic Durability of Rosiglitazone, Metformin, or Glyburide Monotherapy - N Engl J Med. 2006 Dec 4- "Kaplan-Meier analysis showed a cumulative incidence of monotherapy failure at 5 years of 15% with rosiglitazone, 21% with metformin, and 34% with glyburide. This represents a risk reduction of 32% for rosiglitazone, as compared with metformin, and 63%, as compared with glyburide (P<0.001 for both comparisons). The difference in the durability of the treatment effect was greater between rosiglitazone and glyburide than between rosiglitazone and metformin. Glyburide was associated with a lower risk of cardiovascular events (including congestive heart failure) than was rosiglitazone (P<0.05), and the risk associated with metformin was similar to that with rosiglitazone. Rosiglitazone was associated with more weight gain and edema than either metformin or glyburide but with fewer gastrointestinal events than metformin and with less hypoglycemia than glyburide"
• Effects of rosiglitazone and pioglitazone combined with metformin on the prothrombotic state of patients with type 2 diabetes mellitus and metabolic syndrome - J Int Med Res. 2006 Sep-Oct;34(5):545-55 - "In patients with type 2 diabetes mellitus and metabolic syndrome, the combination of metformin plus thiazolidinediones improved glycaemic control and produced a slight but significant reduction in plasminogen activator inhibitor-1 levels"
• An open-label pilot study of the combination therapy of metformin and fluoxetine for weight reduction  - Int J Obes (Lond). 2006 Sep 12 - "In a 6.68-month period, a 7.89 kg decrease in weight (9.32%) and a 3.43 U decrease in BMI (10.14%) were observed in participants of the case group that was statistically significant"
• Improvement in glycaemic control with rosiglitazone/metformin fixed-dose combination therapy in patients with type 2 diabetes with very poor glycaemic control - Diabetes Obes Metab. 2006 Nov;8(6):643-649 - "Unless tolerability issues arose, eligible patients initiated RSG/MET 4 mg/1000 mg fixed-dose combination therapy and were up-titrated in increments of 2 mg/500 mg at 4-week intervals to a daily dose of 8 mg/2000 mg or the maximum tolerated dose ... At week 24, clinically significant mean reduction in A1c from 11.8 to 7.8% (mean reduction, 4.0 +/- 2.2%; p < 0.0001) and mean FPG reduction from 16.9 to 9.2 mmol/l (mean reduction, 7.7 +/- 4.4 mmol/l; p < 0.0001) were observed"
• Risk factors of vitamin B12 deficiency in patients receiving metformin - Arch Intern Med. 2006 Oct 9;166(18):1975-9 - "Each 1-g/d metformin dose increment conferred an odds ratio of 2.88 (95% confidence interval, 2.15-3.87) for developing vitamin B(12) deficiency" - See vitamin B12 at Amazon.com.
• Adherence to Preventive Medications: Predictors and outcomes in the Diabetes Prevention Program - Diabetes Care. 2006 Sep;29(9):1997-2002 - "There was a 38.2% risk reduction for developing diabetes for those adherent to metformin compared with those adherent to placebo" - See metformin at OffshoreRx1.comor SuperSaverMeds.com (Glucophage).
• Metformin improves endothelial vascular reactivity in first-degree relatives of type 2 diabetic patients with metabolic syndrome and normal glucose tolerance - Diabetes Care. 2006 May;29(5):1083-9 - "The metformin group had decreased weight, BMI, systolic blood pressure, and FPG and improved lipid profile. Endothelium-dependent FBF responses were also improved, without any effect on endothelium-independent responses"
• Currently listed contraindications to the use of metformin - more harmful than beneficial? - Dtsch Med Wochenschr. 2006 Jan 20;131(3):105-10 - "As the incidence of lactic acidosis in patients with type 2 diabetes is the same with or without metformin therapy (about 9 per 100000 patient years) there is no evidence that metformin therapy is associated with an increased risk of lactic acidosis ... The two groups did not differ with regard to progression of renal failure, patient-oriented endpoints or overall mortality ... On the basis of the current data, advanced age per se, mild renal impairment and stable heart failure can no longer be upheld as contraindications to the use of metformin"
• Metformin revisited: re-evaluation of its properties and role in the pharmacopoeia of modern antidiabetic agents - Diabetes Obes Metab. 2005 Nov;7(6):654-65 - "Metformin acts by increasing tissue sensitivity to insulin, principally in the liver. Beneficial properties of metformin include weight reduction, favourable effects on the lipid profile and the fibrinolytic pathway, and improvement of ovarian function in some insulin-resistant women. It does not cause hyperinsulinaemia or hypoglycaemia" - See Glucophage at SuperSaverMeds.com or OffshoreRx1.com.
• Metformin decelerates aging and development of mammary tumors in HER-2/neu transgenic mice - Bull Exp Biol Med. 2005 Jun;139(6):721-3 - "Mean life span of mice increased by 8% (p<0.05), in 10% long-living mice it was prolonged by 13.1%, and the maximum life span was prolonged by 1 month under the effect of metformin in comparison with the control. The rate of populational aging decreased by 2.26 times ... Hence, we first demonstrated a geroprotective effect of metformin and its suppressive effect towards the development of mammary tumors"
• The impact of antidiabetic therapies on cardiovascular disease - Curr Atheroscler Rep. 2005 Feb;7(1):50-7 - "Metformin is the only oral antidiabetic medication shown to decrease cardiovascular events independent of glycemic control. Thiazolidinediones improve insulin resistance and lower insulin concentrations, which is beneficial because hyperinsulinemia is an independent predictor of cardiovascular disease"
• Metformin and weight loss in obese women with polycystic ovary syndrome (PCOS): comparison of doses - J Clin Endocrinol Metab. 2005 May 10 - "the Ob sub-group showed a dose relationship (1.5 Kg [3.3 lbs] and 3.6 Kg [7.9 lbs] in 1500 mg and 2550 mg groups respectively ... Suppression of androstenedione was significant with both metformin doses" - See metformin at The Antiaging Store.
• Intensive Lifestyle Intervention or Metformin on Inflammation and Coagulation in Participants With Impaired Glucose Tolerance - Diabetes. 2005 May;54(5):1566-1572 - "In men, the median changes in CRP from baseline to 1 year were -33% in the lifestyle group, -7% in the metformin group, and +5% in the placebo group. In women, the changes in CRP from baseline to follow-up were -29% in the lifestyle group, -14% in the metformin group, and 0% in the placebo group"
• Administration of B-group vitamins reduces circulating homocysteine in polycystic ovarian syndrome patients treated with metformin: a randomized trial - Hum Reprod. 2005 Mar 24 - "These findings suggest that B-group vitamins and folic acid administration counteract the Hcy-increasing effect seen with metformin therapy"
• Effects of metformin on the body composition in subjects with risk factors for type 2 diabetes - Diabetes Obes Metab. 2005 Mar;7(2):189-92 - "In the metformin group, there was a decrease in fat weight from 25.9 +/- 9.4 to 20.8 +/- 9.2 kg, p < 0.01, an increase in lean weight from 57.05 +/- 13.6 to 61.9 +/- 16.5 kg, p < 0.01, an increase in basal metabolism from 1735 +/- 413 to 1878 +/- 505 calories/day, p < 0.05 and an increase in body water" - See metformin at IAS or OffshoreRx1.com.  Note:  That's a 19.7% decrease in fat (25.9-20.8)/25.9 = 19.7%, a 8.5% increase in lean weight (61.9-57.05)/57.05 = 8.5% and a 8.2% increase in basal metabolism (1878-1735)/1735 = 8.2%. - Ben
• Metformin or gliclazide, rather than glibenclamide, attenuate progression of carotid intima-media thickness in subjects with type 2 diabetes - Diabetologia. 2004 Nov 24 - "These data indicate that metformin or gliclazide, rather than glibenclamide, have a potent anti-atherogenic effect in type 2 diabetes"
• Metformin: drug of choice for the prevention of type 2 diabetes and cardiovascular complications in high-risk subjects - Diabetes Metab. 2003 Sep;29(4):121-2 - "Metformin is unique in being not only as effective as any other oral antidiabetic therapy in controlling blood glucose, but also having an unparalleled clinical database relating to improved clinical outcomes in pre-diabetic subjects, and patients with established type 2 diabetes"
• Potential contribution of metformin to the management of cardiovascular disease risk in patients with abdominal obesity, the metabolic syndrome and type 2 diabetes - Diabetes Metab. 2003 Sep;29(4):53-61 - "metformin has been shown to not only contribute to a better glycaemic control but also to induce some weight loss (especially in the visceral depot) which may contribute to the improvement of the features of the metabolic syndrome. Thus, metformin treatment may represent a relevant element of an integrated lifestyle modification-pharmacotherapy to prevent not only type 2 diabetes but also cardiovascular disease"
• Do effects on blood pressure contribute to improved clinical outcomes with metformin? - Diabetes Metab. 2003 Sep;29(4):62-70 - "Metformin improves insulin sensitivity in liver and muscle as its primary antihyperglycaemic mechanism of action, and intensive glycaemic management with metformin significantly reduced the risk of macrovascular diabetic complications in the UK Prospective Diabetes Study. The clinical outcome benefits in the metformin group included a significant reduction in the risk of stroke (- 41% vs + 14% with sulphonylurea or insulin treatment, p=0.032) ... metformin significantly improved endothelial function, a key regulator of vascular tone and blood pressure, in type 2 diabetic patients"
• The potential of metformin for diabetes prevention - Diabetes Metab. 2003 Sep;29(4):104-11 - "Treatment with metformin significantly reduced the incidence of diabetes in subjects with IGT and high-normal fasting plasma glucose in the DPP. Moreover, metformin was well tolerated, and health economic analyses suggest that metformin treatment is cost-effective in the US and Europe ... The results of the DPP identify metformin as an effective option for the prevention of diabetes in subjects with IGT and impaired fasting glucose"
• Beneficial effects of metformin on haemostasis and vascular function in man - Diabetes Metab. 2003 Sep;29(4):44-52 - "Metformin is a biguanide compound which is antihyperglycaemic, reduces insulin resistance and has cardioprotective effects on lipids, thrombosis and blood flow. Metformin has a weight neutral/weight lowering effect and reduces hypertriglyceridaemia, elevated levels of PAI-1, factor VII and C-reactive protein. In addition recent studies indicate that metformin has direct effects on fibrin structure/function and stabilises platelets, two important components of arterial thrombus. The United Kingdom Prospective Diabetes Study (UKPDS) reported that metformin was associated with a 32% reduction in any diabetes related endpoint (p<0.002), a 39% reduction in myocardial infarction (p<0.01) and a non-significant 29% fall in microvascular complications. The figures for macrovascular complications compare favourably for those described for other cardioprotective agents such as ACE inhibitors and statins. These findings confirm metformin as first line therapy in the management of obese insulin resistant type 2 diabetes and in the prevention of the vascular complications of this common condition"
• Effect of metformin on insulin sensitivity and insulin secretion in female obese patients with normal glucose tolerance - Diabetes Metab 2003 Apr;29(2 Pt 1):125
• Effect of metformin and sulfonylurea on C-reactive protein level in well-controlled type 2 diabetics with metabolic syndrome - Endocrine 2003 Apr;20(3):215-8 - "CRP level was significantly lower in patients using metformin for blood glucose control compared with those using glibenclamide, 5.56 and 8.3 mg/L, respectively ... The data showed that metformin decreases the level of circulating CRP, a marker of inflammation, more than glibenclamide"
• What to Do About the Metabolic Syndrome? - Archives of Internal Medicine, 2/24/03 - "Substantial data are accumulating to suggest that lifestyle modification aimed at producing weight loss is an effective treatment for overweight or obese individuals with the metabolic syndrome ... Some physicians prescribe metformin because it can be associated with weight reduction and seems to counteract insulin resistance. However, metformin is not approved by the Food and Drug Administration as a weight loss drug ... Some might consider the use of weight loss drugs in patients with metabolic syndrome"
• Metformin-Associated Vitamin B12 Deficiency - Archives of Internal Medicine, 10/28/02
• Evaluation of the safety and efficacy of sibutramine, orlistat and metformin in the treatment of obesity - Diabetes Obes Metab. 2002 Jan;4(1):49-55 - "sibutramine, orlistat and metformin are all effective and safe medications that reduce cardiovascular risk and can decrease the risk of type 2 diabetes mellitus in obese females. Overall, treatment with 10mg sibutramine bid is more effective than orlistat or metformin therapy in terms of weight reduction"