Recent Longevity News for the seven days ending 5/22/13.  You should consult your doctor if you are taking any medications.

Mediterranean diet seems to boost aging brain power - Science Daily, 5/21/13 - "Participants, who were all taking part in the PREDIMED trial looking at how best to ward off cardiovascular disease, were randomly allocated to a Mediterranean diet with added olive oil or mixed nuts or a control group receiving advice to follow the low-fat diet typically recommended to prevent heart attack and stroke ... After an average of 6.5 years, they were tested for signs of cognitive decline using a Mini Mental State Exam and a clock drawing test ... The average scores on both tests were significantly higher for those following either of the Mediterranean diets compared with those on the low fat option"

Anabolic steroids may affect future mental health - Science Daily, 5/20/13 - "The study included almost 700 former Swedish wrestlers, weightlifters, powerlifters and throwers who competed at the elite level sometime between 1960 and 1979 ... We found a clear link. AAS users were more likely to have been treated for depression, concentration problems and aggressive behaviour"

Extra Vitamin D May Ease Crohn's Symptoms, Study Finds - WebMD, 5/20/13 - "Extra vitamin D "was associated with significantly less physical, emotional and general fatigue, greater quality of life and the ability to perform activities of daily living," ... evaluated 27 patients who had Crohn's in remission. (Even in remission, fatigue and quality of life can be problematic.) The patients were assigned to take either 2,000 IUs (international units) of vitamin D a day or a dummy vitamin for three months" - See vitamin D at Amazon.com.

Sugar-sweetened beverages associated with increased kidney stone risk - Science Daily, 5/15/13 - "Twenty percent of American males and 10 percent of American females will experience a kidney stone at some point in their lifetime ... They found that participants who consumed one or more sugar-sweetened cola servings per day had a 23 percent higher risk of developing kidney stones compared with those participants consuming less than one serving per week. This was true for consuming sugar-sweetened non cola as well, such as punch. They also found that some beverages, such as coffee, tea and orange juice, were associated with a lower risk of stone formation"

Dietary Intake of Saturated Fatty Acids and Incident Stroke - Medscape, 5/15/13 - "We sought to test the hypothesis that SFA intake is associated inversely with risk of stroke and its subtypes and positively with coronary heart disease among Japanese, whose average SFA intake is lower than that of Westerners ... We found inverse associations between SFA intake and total stroke [multivariable hazard ratio (95% confidence interval) for the highest vs. lowest quintiles = 0.77 (0.65–0.93), trend P = 0.002], intraparenchymal haemorrhage [0.61 (0.43–0.86), P for trend = 0.005], and ischaemic stroke [0.84 (0.67–1.06), trend P = 0.08], primarily for deep intraparenchymal haemorrhage [0.67 (0.45–0.99), P for trend = 0.04] and lacunar infarction [0.75 (0.53, 1.07), trend P = 0.02]. We also observed a positive association between SFAs intake and myocardial infarction [1.39 (0.93–2.08), trend P = 0.046] primarily among men. No associations were observed between SFAs intake and incidence of subarachnoid haemorrhage or sudden cardiac death" - Note:  So maybe moderation is the key.

Fish oil may stall effects of junk food on brain - Science Daily, 5/14/13 - "high-fat diets could disrupt neurogenesis, a process that generates new nerve cells, but diets rich in omega-3s could prevent these negative effects by stimulating the area of the brain that control feeding, learning and memory ... Excessive intake of certain macronutrients, the refined sugars and saturated fats found in junk food, can lead to weight gain, disrupt metabolism and even affect mental processing ... These changes can be seen in the brain's structure, including its ability to generate new nerve cells, potentially linking obesity to neurodegenerative diseases ... omega-3 fish oils can reverse or even prevent these effects ... omega-3s restore normal function by interfering with the production of these inflammatory molecules, suppressing triglycerides, and returning these nerve growth factors to normal ... Fish oils don't appear to have a direct impact on weight loss, but they may take the brakes off the detrimental effects of some of the processes triggered in the brain by high-fat diets. They seem to mimic the effects of calorie restrictive diets and including more oily fish or fish oil supplements in our diets could certainly be a positive step forward for those wanting to improve their general health" - See Mega Twin EPA at Amazon.com and Jarrow Max DHA at Amazon.com.

No Benefit in Sharply Restricting Salt, Panel Finds - New York Times, 5/14/13 - "But the new expert committee, commissioned by the Institute of Medicine at the behest of the Centers for Disease Control and Prevention, said there was no rationale for anyone to aim for sodium levels below 2,300 milligrams a day ... One 2008 study the committee examined, for example, randomly assigned 232 Italian patients with aggressively treated moderate to severe congestive heart failure to consume either 2,760 or 1,840 milligrams of sodium a day, but otherwise to consume the same diet. Those consuming the lower level of sodium had more than three times the number of hospital readmissions — 30 as compared with 9 in the higher-salt group — and a more than twice as many deaths — 15 as compared with 6 in the higher-salt group ... Another study ... the risks of heart attacks, strokes, congestive heart failure and death from heart disease increased significantly for those consuming more than 7,000 milligrams of sodium a day and for those consuming less than 3,000 milligrams of sodium a day"

Abstracts from this week's Doctor's Guide Nutrition/Dietetics plus abstracts from my RSS feeds (Click here for the journals, the PubMed ones at the top):

Resveratrol improves learning and memory in normally aged mice through microRNA-CREB pathway - Biochem Biophys Res Commun. 2013 May 15 - "Here we report that, after intraventricular injection of RSV for one week in 8-9 month-old mice, the long-term memory formation and the LTP induction from hippocampus CA1 were improved ... These findings demonstrate a role for RSV in cognition and a microRNA-CREB-BDNF mechanism by which RSV regulates these processes, demonstrating its value as a potential therapeutic target against CNS disorders in aging" - See resveratrol products at Amazon.com.

Intakes of calcium, vitamin D, and dairy servings and dental plaque in older Danish adults - Nutr J. 2013 May 16;12(1):61 - "Intakes of calcium dairy-servings within-recommendations were inversely associated with plaque, among those with higher, but not lower, vitamin D intakes. Due to the cross-sectional nature of the study, it is not possible to infer that this association is causal" - See vitamin D at Amazon.com.

Does vaginal delivery affect postnatal coitus? - Int J Impot Res. 2013 May 16 - "We concluded that vaginal delivery indeed may result in loose vagina compared with cesarean delivery. However, it did not negatively affect the postnatal sexual function. Therefore, women should be assured that their sexual functions won't be affected by the types of delivery"

Effect of serum folate status on total folate and 5-methyltetrahydrofolate in human skin - Am J Clin Nutr. 2013 May 15 - "Total folate (by using a microbiological assay) and 5-MTHF (by using high-pressure liquid chromatography) were measured in fasting serum and fresh skin obtained at surgery by using a recovery validated extraction method ... The high proportion of 5-MTHF in the epidermis, which is further emphasized in subjects with a lower (10-20-nM) serum folate status, points to a special role for this form of folate in skin, perhaps as a protectant from ultraviolet-induced photosensitization reactions. 5-MTHF may also maintain methylation reactions that influence the proliferative activity. These results may help to individualize the treatment of psoriasis patients with methotrexate and folate" - See folic acid products at Amazon.com.

Egg consumption in relation to risk of cardiovascular disease and diabetes: a systematic review and meta-analysis - Am J Clin Nutr. 2013 May 15 - "A systematic literature review was conducted for published studies in PubMed and EMBASE through March 2012 ... This meta-analysis suggests that egg consumption is not associated with the risk of CVD and cardiac mortality in the general population. However, egg consumption may be associated with an increased incidence of type 2 diabetes among the general population and CVD comorbidity among diabetic patients" - Note:  Unless they can figure out a way to filter out how people are cooking those eggs and what they are eating with the eggs, I don't see how the study is useful.  Just think how frying the eggs, eating bacon, sausage, ham, fried hash browns and toast with margarine (hydrogenated oils) or butter can skew the study over just eggs cooked in a microwave with cooking spray.

• Here's what I use sprayed with olive oil.  The secret is that you have to turn it over.  I go 50 seconds on one side and 42 seconds on the other.  Don't wait in-between.
• Chef Buddy Microwave Egg Cooker
• Misto Tritan Oval Oil Sprayer Bottle, White

Low serum levels of 25-hydroxyvitamin D predict hip fracture in the elderly. A NOREPOS study - J Clin Endocrinol Metab. 2013 May 15 - "risk of hip fracture in Norway, a high-latitude country that has among the highest hip fracture rates worldwide ... We observed an inverse association between s-25(OH)D and hip fracture; those with s-25(OH)D in the lowest quartile (<42.2 nmol/l) had a 38% (95% CI 9-74%) increased risk of hip fracture compared with the highest quartile ... In this prospective case-cohort study of hip fractures, the largest ever reported, we found an increased risk of hip fracture in subjects in the lowest compared to the highest quartile of serum 25-hydroxyvitamin D" - See vitamin D at Amazon.com.

C-Reactive Protein, Lipid-soluble Micronutrients, and Survival in Colorectal Cancer Patients - Cancer Epidemiol Biomarkers Prev. 2013 May 15 - "A positive association with overall risk of death was observed for CRP (HR for highest vs. lowest quintile: 1.80; 95% CI: 1.07-3.04; Ptrend=0.01) whereas, inverse associations were generally observed for retinol and carotenoids (HRs for overall risk of death for the highest quintile ranging from 0.5-0.8) ... These observations are consistent with a direct relationship between circulating CRP and overall survival among colorectal cancer patients ... These results, if reproduced, suggest that reduction of inflammation should be explored as a potential complementary treatment strategy"

Lipid content in hepatic and gonadal adipose tissue parallel aortic cholesterol accumulation in mice fed diets with different omega-6 PUFA to EPA plus DHA ratios - Clin Nutr. 2013 Apr 24 - "Dietary ω-6:EPA+DHA ratios did not affect body weight, but lower ω-6:EPA+DHA ratio diets decreased liver lipid accumulation, which possibly contributed to the lower aortic cholesterol accumulation" - See Mega Twin EPA at Amazon.com and Jarrow Max DHA at Amazon.com.

Glycemic Control and Risk of Cardiovascular Disease Hospitalization and All-Cause Mortality - J Am Coll Cardiol. 2013 May - "Compared with patients with mean A1C 7.0%-7.4%, those with mean A1C <6.0% had a 75% increased risk of CVD hospitalization (hazard ratio [HR] 1.68, 95% CI 1.39-2.04, p<0.001) after adjustment for demographic and clinical characteristics. Those with A1C 6.0%-6.4% (1.18, 1.00-1.40, p=0.048) and 6.5%-6.9% (1.18, 1.02-1.37, p=0.031) also had significantly higher risk relative to the reference group of 7.0%-7.4%, as did patients with A1C 8.5%-8.9% (HR 1.55, 1.24-1.94, p<0.001) and >9.0% (HR 1.83, 1.50-2.22, p<0.001). Risk of all-cause mortality was significantly greater than the reference group among A1C categories <6.0%, 6.0%-6.4%, 6.5%-6.9%, and >9.0% ... The relationship between mean A1C and CVD hospitalizations and all-cause mortality is U-shaped, with greater risk at both higher and lower A1C levels"

Neat Tech Stuff / "How To's":

• Square Stand turns your iPad into a cash register, on pre-order for $299 - engadget.com, 5/14/13

Health Focus (Metformin):

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

• metformin at The Antiaging Store

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 The Antiaging Store.
• 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 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"
• 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"
• Pioglitazone and Metformin Similarly Effective in Reducing HbA1c - Medscape, 12/13/04
• 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"
• Metformin May Improve Cardiac Autonomic System Balance in Overweight Patients with Type 2 Diabetes - Doctor's Guide, 3/15/04
• Metformin Improves Metabolic Control and Other Physiologic Variables in Type 2 Diabetes - Doctor's Guide, 2/25/04
• 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 and Carbohydrate-Modified Diet May Help Sustain Weight Loss - Doctor's Guide, 12/16/03
• No Apparent Increased Risk of Lactic Acidosis Found In Type 2 Diabetics Who Take Metformin - Doctor's Guide, 11/25/03
• Metformin May Improve Metabolic Control in Adolescents with Type I Diabetes - Doctor's Guide, 11/21/03
• Metformin Decreases Serum C-Reactive Protein in Women With Polycystic Ovarian Syndrome - Doctor's Guide, 10/28/03
• Metformin Seems to be Effective for Anovulation in Women with Polycystic Ovary Syndrome - Doctor's Guide, 10/27/03
• 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"
• Inappropriate Metformin Use Frequent in Hospitalised Patients - Doctor's Guide, 6/16/03
• 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"
• Pioglitazone/Sulfonylurea And Pioglitazone/Metaformin Combinations Both Effective For Reducing Very Low Density Lipoproteins And Free Fatty Acids - Doctor's Guide, 5/21/03
• Repaglinide + Metformin Superior to Nateglinide + Metformin in Treating Type 2 Diabetes - Doctor's Guide, 5/18/03
• 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"
• Metformin-Glibenclamide Combination Is More Effective Than Monotherapy In Type 2 Diabetes - Doctor's Guide, 4/24/03
• Pioglitazone Improves Insulin Sensitivity Compared To Metformin - Doctor's Guide, 4/22/03
• 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"
• Metformin Concentrations In Erythrocytes Have Clinical Implications - Doctor's Guide, 3/25/03
• 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"

Abstracts:

• 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" - See pioglitazone at OffshoreRx1.com.
• 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)" - See metformin at The Antiaging Store.
• 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"