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> Anti-aging Research > Metformin
Where to purchase Metformin (don't take unless
under a physician's supervision):
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 IAS.
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"
- 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 Still Best as First Type 2 Diabetes Treatment - WebMD, 1/2/17 -
"Metformin, unless contraindicated, is an effective
treatment strategy because it has better effectiveness, is associated with fewer
adverse effects, and is cheaper than most other oral medications ... The
escalating rates of obesity in the U.S. are increasing the incidence and
prevalence of diabetes substantially. Metformin has the added benefit of being
associated with weight loss" - See
metformin at IAS.
Metformin influences nitrogen and urea metabolism - Science Daily, 9/14/16 -
"metformin intake lowers the levels of the harmful LDL
cholesterol by activating the AMPK protein complex ... metformin also modulates
the body's nitrogen and urea metabolism ... the activation of the AMPK pathway
by metformin affects nitrogen and urea metabolism through a further enzyme***,
which thus lowers the citrulline levels ... Accordingly, the scientists suspect
that the additional intake of citrulline could have a positive effect on the
cardiovascular system in patients being treated with metformin" - See
BulkSupplements Pure L-Citrulline Powder at
Older Drug May Help Type 1 Diabetics' Heart Health - WebMD, 9/6/16 -
"An inexpensive medication normally given to people with
type 2 diabetes may help preserve heart health in people with the less common
form of diabetes -- type 1 ... Metformin is the standard first-line treatment
for type 2 diabetes to help bring blood sugar levels down. It also appears to
help repair damaged blood cells by increasing the number of blood vessel
(vascular) stem cells"
Loss and Reduced Android Fat Tissue at 12 Months in EMPOWIR (Enhance the
Metabolic Profile of Women With Insulin Resistance) - WebMD, 8/2/16 -
"carbohydrate-modified diet (CMD) and were then
randomized to one of three arms for 6 months (phase 1): CMD alone (D), or in
combination with metformin (M), or metformin + rosiglitazone (MR), with
rerandomization of the D group to one of the active treatment arms ... Mean
(±SD) BW decreased significantly at 12 months in the M arm: 85.1 ± 8.5 kg to
79.8 ± 9.0 kg (P = .0003), with 54% of variance in weight over time explained by
M treatment. Mean (±SD) percent android fat decreased significantly in the M and
D arms: 53.5 ± 4.8% to 49.3 ± 7.6% (P = .010) and 52.9 ± 6.2% to 48.1 ± 8.7% (P
Which Diabetes Drug Is Best? - WebMD, 7/19/16 - "Metformin,
in the absence of contraindications or intolerability, should be the first-line
agent to treat patients with type 2 diabetes"
Metformin Linked to Lower
Neurodegenerative Disease Risk - Medscape, 6/11/16 -
"The mechanism is unclear, but metformin is known to cross the blood-brain
barrier ... The adjusted incidence of developing one or more neurodegenerative
diseases per 100 person-years was 2.08 for those who never used metformin, 2.47
for those using metformin less than 1 year, 1.61 for less than 2 years, 1.30 for
2 to 4 years, and 0.49 for 4 or more years ... Compared with no metformin, the
hazard ratios for 2 to 4 years of metformin therapy for all neurodegenerative
diseases combined was 0.623 and for 4 or more years 0.216 ... The findings were
also significant for dementia specifically (0.567 at 2–4 years and 0.252 for 4+
years) and for Parkinson's and Alzheimer's diseases only beyond 4 years (0.038
and 0.229, respectively)" - See
metformin at IAS.
Metformin Active in
Reducing Colorectal Polyp Recurrence - Medscape, 4/22/16 -
"they took patients who underwent resection of
polyps/adenomas, and they randomly assigned them to receive a placebo or
low-dose metformin, 250 mg daily. The treatment lasted for 1 year ... there was
a significant reduction in the number of polyps/adenomas in the
metformin-treated group: 38% of patients had recurrent adenomas compared with
57% in the placebo group" - See
metformin at IAS.
Diabetes drug, metformin, lowers risk of heart disease deaths better than
sulfonylureas - Science Daily, 4/20/16 - "A new
analysis of 204 studies involving more than 1.4 million people suggests that
metformin, the most frequently prescribed stand-alone drug for type 2 diabetes,
reduces the relative risk of a patient dying from heart disease by about 30 to
40 percent compared to its closest competitor drug, sulfonylurea ... Among other
findings, the new review revealed that DPP-4 inhibitors, a class of
anti-diabetic drugs that were very new at the time of the 2011 review, were
clearly less effective at lowering blood sugar levels compared to metformin and
Post-menopausal women taking metformin for diabetes may be at lower risk of
cancer - Science Daily, 4/7/16 - "women with
diabetes had a 45% greater risk of death from invasive cancer overall when
compared to women without diabetes. In addition, among women with diabetes, the
risk of cancer death differed significantly between metformin users and
nonusers. The researchers noted a trend of decreasing risk of cancer death with
increasing duration of metformin use ... Compared to women without diabetes,
women with diabetes had a 13% higher risk of developing invasive cancer. These
women also face increased risk that ranges from 20% to nearly double the chances
of being diagnosed with the following cancers: colon, liver, pancreas,
endometrial and non-Hodgkin lymphoma. Results also show that metformin use was
associated with better survival in diabetes patients diagnosed with ovarian,
colorectal and breast cancer" - See
metformin at IAS.
Diabetes Drugs Have
Positive Effect in MS - Medscape, 3/22/16 - "After a
mean follow-up of 26.7 months, patients receiving metformin or pioglitazone had
a significant decrease in the number of new or enlarging T2 lesions on brain MRI
compared with the control group and compared with findings on MRIs performed 2
years before ... This decrease was evident even after 6 months of treatment. The
lowest mean number of new or enlarging T2 lesions occurred after 18 months of
treatment (metformin, 0.5; pioglitazone, 0.6) and remained low throughout the
study ... There was no significant difference between the two treatments ...
Although not designed to detect treatment effects, the study did find that
fasting glucose levels, fasting insulin levels, insulin resistance, total
cholesterol, low-density lipoprotein cholesterol, triglycerides, and systolic
blood pressure all declined significantly in both treatment groups after 12
diabetes drug metformin inhibits progression of pancreatic cancer - Science
Daily, 1/14/16 - "metformin decreases the inflammation
and fibrosis characteristic of the most common form of pancreatic cancer ...
Diabetic patients taking metformin -- a commonly used generic medication for
type 2 diabetes -- are known to have a reduced risk of developing pancreatic
cancer; and among patients who develop the tumor, those taking the drug may have
a reduced risk of death"
study indicates that metformin has the potential to prevent and treat
preeclampsia - Science Daily, 12/22/15 - "the drug
metformin decreases the production of the two toxins elevated in preeclampsia
and also helps heal injured blood vessels ... Metformin appears to be the
aspirin of the 21st century, because the drug has been discovered to have
unexpected health benefits not only in diabetes, but also in polycystic ovarian
disease and recent work has highlighted its anti-cancer properties"
Diabetes Drug Improves Gut Bacteria - WebMD, 12/4/15 -
"taking metformin had positive effects on the intestinal
bacteria of people with type 2 diabetes. Specifically, the drug improved the
ability of the bacteria to produce certain types of short-chain fatty acids that
reduce blood sugar levels in different ways"
Therapies to Treat Alzheimer Disease - Medscape, 8/27/15 -
"There are other treatments, such as metformin and the
new generation of antidiabetic drugs known as incretins, that have been shown in
animal models to have a pro-cognitive effect ... Inflammatory molecules have a
negative effect on the brain and also contribute to insulin resistance"
Metformin May Also Lower
LDL Cholesterol: Study Suggests How - Medscape, 8/13/15 -
"It appears that "metformin intake activates
AMP-activated protein kinase (AMPK) and consequently suppresses fatty-acid
desaturase (FADS) genes, which leads to reduced levels of lipid metabolites and
LDL cholesterol," ... Our study suggests that metformin might indeed have an
additional beneficial effect with regard to cardiovascular diseases among the
[type 2] diabetes patients"
resistance increases risk for Alzheimer's disease, study finds - Science
Daily, 7/27/15 - "examined brain scans in 150 late
middle-aged adults, who were at risk for Alzheimer's disease, but showed no sign
of memory loss. The scans detected if people with higher levels of insulin
resistance used less blood sugar in areas of the brain most susceptible to
Alzheimer's. When that happens, the brain has less energy to relay information
and function ... If you don't have as much fuel, you're not going to be as adept
at remembering something or doing something ... this is important with
Alzheimer's disease, because over the course of the disease there is a
progressive decrease in the amount of blood sugar used in certain brain regions.
Those regions end up using less and less"
medication reduces dementia risk: Analysis of health insurance data suggests
preventive effect - Science Daily, 6/23/15 -
"Treatment with pioglitazone showed a remarkable side benefit. It was able to
significantly decrease the risk of dementia ... The longer the treatment, the
lower the risk ... Risk reduction was most noticeable when the drug was
administered for at least two years ... Metformin -- another frequently
prescribed antidiabetic drug -- also lowered the risk of developing dementia.
However, the effect was lower than that of pioglitazone" - See
metformin at IAS. Pioglitazone is harder to find. I've been
taking both in low dose for years for various anti-aging advantages.
Impact of Metformin on
Clinical Outcomes in Prostate Cancer - Medscape, 6/9/15 -
"Metformin may reduce the risk of biochemical recurrence
in prostate cancer"
Should Antidiabetics Be
Prescribed in Prediabetes? - Medscape, 6/4/15 -
"it's imperative that we talk to the patient about their prediabetes as soon as
their fasting blood glucose level exceeds 100 mg/dL ... As for metformin, based
on the ADA guidelines, we could prescribe it as soon as lifestyle and dietary
maintaining muscle strength while we age - Science Daily, 6/2/15 -
"Previous research by Steinberg's team has shown that
this "metabolic switch" is turned on with exercise as well as commonly-used
medications including metformin and salicylate (the active ingredient in
Aspirin) ... We know we can turn on the AMPK pathway with intense exercise and
commonly-used Type 2 diabetes medications"
Metformin use associated with reduced risk of developing open-angle glaucoma
- Science Daily, 5/28/15 - "patients prescribed the
highest amount of metformin (greater than 1,110 grams in two years) had a 25
percent reduced risk of OAG risk compared with those who took no metformin.
Every one-gram increase in metformin was associated with a 0.16 percent
reduction in OAG risk, which means that taking a standard dose of 2 grams of
metformin per day for two years would result in a 20.8 percent reduction in risk
of OAG ... this study points out the importance of understanding the potential
impact of CR (caloric restriction) mimetic drugs on the risk of developing other
medical conditions that affect older persons"
Metformin Underused in
Patients With Prediabetes - Medscape, 5/1/15 -
"Metformin was prescribed for only 3.7% of patients with prediabetes, even
though it can help prevent the onset of type 2 diabetes ... About one in three
Americans has prediabetes ... clinicians can consider metformin in those with
impaired glucose tolerance, impaired fasting glucose, or an HbA1c of 5.7% to
6.4%" - Note: Plus many use it for anti-aging.
Metformin, vitamin D3 show impressive promise in preventing colorectal cancer
- Science Daily, 3/24/15 - "Not only did the combination
of the two improve outcomes in animal studies, but the dual-compound effect was
dramatically better than either option alone. Even better, these impressive
results required only modest amounts of metformin and Vitamin D3, making
concerns about side effects from mega-dosing entirely moot ... Few colon
neoplasias developed in the animals receiving moderate doses of
metformin-vitamin D combination ... On average, there was also a 40 percent
decrease in the development of polyps in all animals receiving both drugs in
combination compared to the control groups" - See
vitamin D at Amazon.com.
Metformin Beats Other Type 2 Diabetes Drugs for First Treatment: Study – WebMD
- WebMD, 10/28/14 - "of those started on metformin, only
about one-quarter needed another drug to control their blood sugar. However,
people who were started on type 2 diabetes drugs other than metformin often
needed a second drug or insulin to control their blood sugar levels ... around
40 percent of people taking a sulfonylurea, a thiazolidinedione, or a dipeptidyl
peptidase 4 inhibitor (DPP-4 inhibitor) added a second drug to their diabetes
treatment regimen during the study. Just 25 percent of those on metformin added
an additional oral drug during the study period ... 5 percent of those started
on metformin later added insulin to their treatment, according to the study.
About 9 percent of those who started on a sulfonylurea, 6 percent started on a
DPP-4 inhibitor and 6 percent started on thiazolidinediones, also took insulin"
Metformin and Lower AF Risk
Among Patients With T2DM - Medscape, 10/13/14 -
"After adjusting for co-morbidities and medications, metformin independently
protected the diabetic patients from new-onset AF with a hazard ratio of .81
(95% confidence interval 0.76–0.86, p < 0.0001). Metformin significantly
decreased the extent of pacing-induced myolysis and the production of reactive
oxygen species" - [Abstract]
metformin at IAS.
Prediabetes increases the risk of cancer by 15 percent, study of almost 900,000
people shows - Science Daily, 9/8/14 - "after
controlling for BMI, the presence of prediabetes remained associated with an
increased risk of cancer of 22% ... In a site-specific cancer analysis,
prediabetes was significantly associated with increased risks of cancer of the
stomach/colorectum (relative risk, RR 1.55), liver (RR 2.01), pancreas (RR
1.19), breast (RR 1.19) and endometrium (RR 1.60) (all statistically
significant), but not associated with cancer of the bronchus/lung, prostate,
ovary, kidney or bladder ... several possible mechanisms could explain the
results. First, chronic hyperglycaemia and its related conditions, such as
chronic oxidative stress and the accumulation of advanced glycated endproducts
(that are made in conditions of excessively high blood sugar) may act as
carcinogenic factors. Second, increased insulin resistance leads to increased
insulin secretion, which can in turn allow cancer cells to grow and divide ...
It should be noted that metformin -- one of several first line therapies
available to treat type 2 diabetes -- is now considered as having some
'protective' anticancer properties. Notably, metformin mediates an approximately
30% reduction in the lifetime risk of cancer in diabetic patients. However,
whether this is true in prediabetic individuals is not yet known"
Lifestyle, Metformin, Can
Delay Diabetes, 15-Year DPP Data Show - Medscape, 6/16/16 -
"randomizing overweight or obese people at high risk for
type 2 diabetes to intensive lifestyle change or giving them the oral agent
metformin can reduce or delay the development of the disease for as long as 15
years, in some cases ... In 2002, the results of the DPP were reported in the
New England Journal of Medicine and showed a dramatic 58% reduction in new type
2 diabetes with the intensive lifestyle intervention and a 31% reduction with
metformin compared with controls, in both men and women, across a broad spectrum
of races, and across age groups, including the elderly ... He listed a myriad of
other conditions that occur more frequently in diabetes, such as cirrhosis,
cancer, cognitive decline, depression, sleep apnea, gut problems, fractures, and
sexual dysfunction, and noted that diabetes is really "accelerated aging.""
Anti-diabetic drug slows aging and lengthens lifespan, animal study suggests
- Science Daily, 6/2/14 - "Metformin causes a slight
increase in the number of harmful oxygen molecules. We found that this makes
cells stronger and extends their healthy lifespan ... Other studies in humans
have shown that metformin suppresses some cancers and heart disease. Metformin
could even be an effective drug for counteracting the general effects of aging,
say the researchers" - [Abstract]
explains action of drug that may slow aging, related disease - Science
Daily, 5/20/14 - "Rapamycin, an antibiotic and
immunosuppressant approved for use about 15 years ago, has drawn extensive
interest for its apparent ability -- at least in laboratory animal tests -- to
emulate the ability of dietary restriction in helping animals to live both
longer and healthier ... this medication has some drawbacks, including an
increase in insulin resistance that could set the stage for diabetes ... a
combination of rapamycin and another drug to offset that increase in insulin
resistance might provide the benefits of this medication without the unwanted
side effect ... Laboratory mice that have received rapamycin have reduced the
age-dependent decline in spontaneous activity, demonstrated more fitness,
improved cognition and cardiovascular health, had less cancer and lived
substantially longer than mice fed a normal diet ... the drug metformin can
address that concern"
Metformin Linked to Reduced
Risk for Glaucoma - Medscape, 5/13/14 - "The risk
for open-angle glaucoma was 25% lower in patients with documented cumulative
metformin use of more than 1110 g over 2 years (average dose, 2 g/day) than in
those with no metformin use ... The association was dose-dependent, with a 0.01%
reduced hazard for open-angle glaucoma with every 1 g increase in metformin ...
The greatest risk reduction was associated with the highest baseline risk and
the highest glycated hemoglobin (HbA1c) levels ... The findings support the
concept that metformin and some other drugs are geroprotective because they
produce effects that mimic caloric restriction"
Should Patients Taking
Metformin Also Take Vitamin B12? - Medscape, 12/13/13 -
"Vitamin B12 deficiency is estimated to be present in up
to 30% of patients with diabetes taking metformin. The risk for vitamin B12
deficiency increases with patient age and the dose and duration of metformin
use.[5,7] Concomitant conditions such as suboptimal dietary intake, which is
common among vegetarians and alcohol abusers, and malabsorption due to atrophic
gastritis, pernicious anemia, chronic pancreatitis, and celiac disease may
further increase risk for vitamin B12 deficiency. The combination of
metformin with proton pump inhibitors has been reported to have an additive
effect on risk for vitamin B12 deficiency ... Screening for vitamin B12
deficiency seems reasonable for all adult patients with diabetes, especially
those taking metformin" - See
vitamin B12 at Amazon.com.
Some Diabetes Drugs May Affect Cancer Risk in Women - WebMD, 12/6/13 -
"Cleveland Clinic researchers analyzed data from more
than 25,600 women and men with type 2 diabetes ... The drugs included "insulin
sensitizers," which lower blood sugar and insulin levels in the body by
increasing the muscle, fat and liver's response to insulin. The other drugs
analyzed were "insulin secretagogues," which lower blood sugar by stimulating
beta cells in the pancreas to make more insulin ... The use of insulin
sensitizers in women was associated with a 21 percent decreased cancer risk
compared to insulin secretagogues, the investigators found. Furthermore, the use
of a specific insulin sensitizer called thiazolidinedione was associated with a
32 percent decreased cancer risk in women compared to sulphonylurea, an insulin
secretagogue ... there were no significant differences between men who used
insulin sensitizers or secretagogues"
Scientists unlock secrets of diabetes drug - Science Daily, 11/3/13 -
"The key is that metformin doesn't work to lower blood
glucose by directly working on the glucose. It works on reducing harmful fat
molecules in the liver, which then allows insulin to work better and lower blood
sugar levels ... Fat is likely a key trigger for pre-diabetes, causing blood
sugar to start going up because insulin can't work as efficiently to stop sugar
coming from the liver"
drug with chemo, radiation may improve outcomes for lung cancer - Science
Daily, 10/23/13 - "Treating aggressive lung cancer with
the diabetes drug metformin along with radiation and chemotherapy may slow tumor
growth and recurrence ... Metformin, the most-widely used drug for type-2
diabetes, has been shown to have anti-cancer effects on a number of cancers,
including prostate and colon"
Common Diabetes Drugs May Carry Risk, Study Suggests - WebMD, 9/26/13 -
"Both metformin (brand names include Glucophage and
Fortamet) and sulfonylureas (glyburide and glipizide) are commonly prescribed as
first-line therapies for patients and have been available since the 1950s ...
Patients who took sulfonylureas only were 58 percent more likely to die from any
cause than those who took metformin only ... Sulfonylureas work "by increasing
insulin release from the beta cells in the pancreas," while metformin "acts by
suppressing glucose production by the liver,""
Metformin Use and Risk of Prostate Cancer - Medscape, 9/13/13 -
"This large study did not find an association between
metformin use and risk of prostate cancer among older men with diabetes,
regardless of cancer grade or method of diagnosis" - Note: I usually
don't publish studies that don't show anything but people might see the
headlines elsewhere and think otherwise on this one with the way it's worded.
Metformin May Lower Risk of Prostate Cancer Death, Researchers Say - WebMD,
8/5/13 - "metformin is associated with improved survival
among diabetic patients with prostate cancer ... whether metformin can prevent
prostate cancer progression in people without diabetes remains to be seen ...
those who took metformin had a 24 percent reduction in risk from prostate cancer
death for every additional six months of use after their cancer diagnosis. The
risk reduction of death from other causes was initially the same but declined
over time ... No reduction in death risk was seen for patients taking any other
diabetes drug ... other diabetes drugs work by increasing the body's insulin
production, metformin is an "insulin sensitizer" that works by making the body
more sensitive to the insulin already produced ... Some research suggests that
high insulin levels can influence cancer growth. Metformin, by not increasing
the body's insulin production, may decrease cancer cells' growth, some experts
say" - Note: Metformin is another one that I take in low dose for
Pill linked to long life in
mice - BBC News, 7/31/13 - "Scientists believe the
drug, metformin, may mimic the effects of extreme calorie restriction ...
Metformin is one of the most widely prescribed treatments for type-2 diabetes,
which occurs mainly in people above the age of 40. It is also used to treat
metabolic syndrome, a combination of diabetes, high blood pressure and obesity
... The scientists gave one of two different doses of metformin to middle-aged
male mice and found that lower doses increased lifespan by about 5%, and also
delayed the onset of age-associated diseases" - Note: I've been taking
it in low doses for years to help combat aging.
Diabetes Drug May Protect the Brain - WebMD, 7/15/13 -
"Metformin makes muscle tissue more receptive to
insulin, a hormone necessary for sugar (glucose) to get into the body's cells
and tissues to provide fuel. It also decreases the amount of glucose made in the
liver. Sulfonylureas stimulate the production of insulin. TZDs make muscle and
fat tissue more receptive to insulin, and they decrease the amount of glucose
made in the liver ... Compared to people taking sulfonylureas, those on
metformin had a 20 percent decreased risk of developing dementia, according to
the study. There was no difference in dementia risk for those on TZDs or insulin
compared to those on sulfonylureas ... one theory stemming from animal research
is that metformin may play a role in the development of new brain cells
(neurogenesis). It has also been linked to reduced inflammation ... A drug like
metformin, [which is] an insulin sensitizer in the body, may also be an insulin
sensitizer in the brain" - See
metformin at IAS.
CVD Reduced With Metformin,
Higher With Rosiglitazone - Medscape, 6/24/13 - "In
29 different studies, metformin was associated with a 10% reduction in the risk
of cardiovascular events, with the drug associated with a 10% reduction in the
risk of heart failure in seven studies and a 12% reduction in the risk of MI in
nine studies. In contrast, rosiglitazone was associated with a 21% increased
risk of cardiovascular events in 25 studies, a 27% increased risk of heart
failure in 13 studies, and a 17% increased risk of MI in 21 studies"
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 IAS.
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"
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
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 IAS.
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
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"
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.
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
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
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"
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
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
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.
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"
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
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
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
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
'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"
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%"
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
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.
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.
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
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
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"
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,
"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"
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
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
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
- Vitamin B12 Status of
Patients Treated With Metformin - Medscape, 2/17/05 -
"Patients exposed to long-term metformin therapy had
26.7% lower cobalamin, 21.6% lower holotranscobalamin and 9.7% higher HCy
serum concentrations than control subjects. Such changes indicate a
potential risk for development of vitamin B12 deficiency"
Research Highlights Hormonal Control of Cardiovascular Functions -
Doctor's Guide, 8/17/04 -
"The Patients who received metformin experienced an
improvement in several endothelial function markers, including weight,
fasting plasma glucose, soluble intercellular adhesion molecule and soluble
vascular cell adhesion molecule"
Metformin Shows Promise for Diabetes Prevention, but Further Studies Needed
- Doctor's Guide, 6/24/04 -
"After 1 year of treatment, patients receiving
metformin experienced a significantly lower increase in fasting blood
glucose levels compared with the placebo group (3.6 mg/dL vs. 7.2 mg/dL, P <
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"
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
What You Don’t Know About Blood Sugar - Life Extension Magazine, 1/04 -
"it now appears that optimal fasting blood glucose
levels should probably be under 86 mg/dL ...
Chromium supplements have been shown to reduce blood glucose
significantly.70-74 The dose used in human studies ranges from 200 to 1000
mcg of elemental chromium a day, with best results occurring when 400 mcg or
more of chromium is taken daily ... Nondiabetics using metformin may start
off at 500 mg a day and gradually build up to 1000-1500 mg a day. The
objective is not to take so much metformin as to induce a hypoglycemic
state" - See
iHerb chromium products.
Metformin Treatment Leads to Increased Homocysteine, Decreased Vitamin B12
and Folate in Type 2 Diabetes Patients - Doctor's Guide, 10/20/03 -
"Homocysteine requires folate and vitamin B12 to be
properly metabolised, and serum vitamin B12 levels are known to decrease
during metformin treatment ... compared with placebo, metformin was
associated with an increase in serum homocysteine levels (4% [0.2 to 8 µmol
L-1]; P=0.039), and decreases in vitamin B12 (-14% [-4.2 to -24 pmol L-1];
P<0.0001) and folate (-7%"
Uses of Metformin May Extend Beyond Patients with Type 2 Diabetes -
Doctor's Guide, 9/4/03 -
"In type 2 diabetics, metformin appears to decrease
plasma fasting glucose and HbA1c levels without
causing weight gain. Metformin may also have a positive influence on a
variety of cardiovascular risk factors and may be useful in preventing
diabetes in overweight individuals with mild hyperglycaemia ... while
further study is necessary before more widespread use is encouraged, the
role of metformin may be expanded for glucose control in children and
teenagers with type 2 diabetes, in non-diabetic women with PCOS, and to
prevent progression to diabetes"
FDA Approves New Avandamet (Rosiglitazone Maleate/Metformin) Dosage
Strengths For Treatment Of Type 2 Diabetes - Doctor's Guide, 8/27/03
Lifestyle Modification, Metformin Effective Prevention for Type 2 Diabetes
- Doctor's Guide, 7/31/03 -
"1,073 patients were prescribed 850 mg metformin
twice daily, 1,082 had placebo twice daily, and 1,079 were prescribed an
intensive program of lifestyle modification ... Incidence of
diabetes was 58% lower ... in the lifestyle intervention group and 31%
lower ... in the metformin group than in the placebo group"
BioMarker Pharmaceuticals Develops Anti-Aging Therapy - LE Magazine
cover story, 6/03 -
"The BioMarker scientists found that all the
glucoregulatory agents reproduced some of the gene expression effects of CR
[calorie restriction], but that metformin was
the undisputed star of the group, being twice as effective as the others in
reproducing the effects of CR"
Benfluorex Improves Glycaemic Control In Type 2 Diabetes - Doctor's
Guide, 4/29/03 -
"Although benfluorex may be less potent than
metformin, it lowers haemoglobin A1C (HbA1C) and fasting plasma glucose
levels and is well tolerated"
Combination Therapy Improves Management of Obese Diabetics - Doctor's
Guide, 4/15/03 -
insulin-sensitising thiazolidinedione drug, to metformin, a biguanide agent,
greatly enhances the management of obese type 2
diabetic patients who are inadequately controlled by metformin alone"
Diabetes Prevention Efforts Achieving Good Results - Doctor's Guide,
"Strategies that may prevent progression to
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
- Will New Drugs
Head Off Diabetes? - WebMD, 5/10/02 -
""We think of IGT [impaired glucose tolerance] and
diabetes as parts of what we call the metabolic
syndrome. This is something that affects one in four Americans -- and up
to half of the U.S. population by age 60. What we have to target is high
blood sugar, whether it is IGT or type 2 diabetes." ... One diabetes drug,
Glucophage, has already been shown to help prevent type 2 diabetes in people
with IGT. But that same study, published in the February 2002 issue of The
New England Journal of Medicine, showed that exercise was even better than
Glucophage at preventing diabetes"
- The Skinny on Fat
Drugs - WebMD, 2/20/02 -
"This diabetes drug improves sensitivity to insulin.
It seems to prevent weight gain in adults. Studies are under way in
overweight people who do not have diabetes. Side effects of Glucophage
include nausea, flatulence, bloating, and diarrhea at the beginning of
treatment. It can also cause a serious problem -- lactic acidosis -- in some
patients with underlying disease"
- How to Stop
Diabetes In Its Tracks - WebMD, 2/6/02 -
"the study found that the diet/exercise program cut
diabetes risk by 58%. Glucophage was significantly less effective, but still
decreased risk by 31% ... The diet was centered around lowering fat intake
to less than 25% of overall calories ... the 30-minute daily exercise regime
"should be easily achievable" by most nondiabetic overweight Americans with
high blood sugar levels"
Metformin Appears Suitable For Children With Type 2 Diabetes - Doctor's
- Diabetes Drug
[Glucophage/metformin] May Fight Obesity - WebMD, 12/26/01 -
"Pediatricians at the University of Tennessee School
of Medicine put 24 obese adolescents on a low-calorie diet: 1,500 calories a
day for the girls and 1,800 calories a day for the boys. They also gave half
the teens Glucophage and half a placebo ... After eight weeks, dieting teens
who took the placebo lost 3.8 % of their body weight. But those taking
Glucophage lost 6.5 % of their body weight -- nearly twice as much"
The Multiple Benefits of Metformin - Life Extension Magazine, 9/01 -
"An ideal anti-diabetic drug would enhance cellular
insulin sensitivity, inhibit excess intestinal absorption of sugar, reduce
excess liver production of glucose, promote weight loss and reduce
cardiovascular risk factors. Metformin (Glucophage) is the one drug that
does all of this and more"
- How to Avoid
Diabetes -- Landmark Results Unveiled - WebMD, 8/8/01 -
"Either a low-fat diet combined with moderate
exercise or the drug metformin -- brand name Glucophage -- dramatically
reduced type 2 diabetes risk among overweight people with elevated blood
Differential effects of
metformin on age related comorbidities in older men with type 2 diabetes - J
Diabetes Complications. 2017 Jan 28 - "age-related
comorbidity (ARC) ... frailty-related diseases (FRD) ... 'Healthy Class'
(53.6%): metformin reduced likelihoods of all ARCs (from 0.14% in dementia to
6.1% in CVD). 'High Cancer Risk Class' (11.6%): metformin reduced likelihoods of
CVD (13.3%), cancer (45.5%), depression (5.0%), and FRD (13.7%). 'High CVD Risk
Class' (17.4%): metformin reduced likelihoods of CVD (48.6%), cancer (3.2%),
depression (2.8%), and FRD (6.3%). 'High Frailty Risk Class' (17.2%): metformin
reduced likelihoods of CVD (18.8%), cancer (3.9%), dementia (3.8%), depression
(15.6%), and FRD (23.8%)" - See
metformin at IAS.
castration-induced EMT in prostate cancer by repressing COX2/PGE2/STAT3 axis
- Cancer Lett. 2016 Dec 30;389:23-32 - "We propose that
metformin represses prostate cancer EMT and metastasis through targeting the
COX2/PGE2/STAT3 axis. These findings suggest that metformin by itself or in
combination with other anticancer drugs could be used as an anti-metastasis
Effects of metformin on
blood pressure in nondiabetic patients: a meta-analysis of randomized controlled
trials - J Hypertens. 2016 Sep 7 - "Pooled results
showed that metformin had a significant effect on SBP (mean difference
-1.98 mmHg; 95% confidence interval -3.61, -0.35; P = 0.02), but not on DBP
(mean difference -0.67 mmHg; 95% confidence interval -1.74, 0.41; P = 0.22). In
subgroup analysis, we found that the effect of metformin on SBP was significant
in patients with impaired glucose tolerance or obesity (BMI ≥30 kg/m), with a
mean reduction of 5.03 and 3.00 mmHg, respectively"
Activation of the
AMPK/Sirt1 pathway by a leucine-metformin combination increases insulin
sensitivity in skeletal muscle, and stimulates glucose and lipid metabolism and
increases life span in Caenorhabditis elegans - Metabolism. 2016 Jul 9 -
"We have previously shown leucine (Leu) to activate
Sirt1 by lowering its KM for NAD+, thereby amplifying the effects of other
sirtuin activators and improving insulin sensitivity. Metformin (Met) converges
on this pathway both indirectly (via AMPK) and by direct activation of Sirt1 ...
Leu and Met synergize to enable Sirt1 activation at low NAD+ concentrations
(typical of energy replete states). Sirt1 and AMPK activations are required for
Met-Leu's full action, which result in improvements in energy metabolism and
insulin sensitivity" - See BulkSupplements Pure L-Leucine Powder (1 Kilogram)
Metformin at IAS.
cortisol regeneration by 11βHSD1 in obese men with and without type 2 diabetes
mellitus - J Clin Endocrinol Metab. 2016 Jul 26 -
"Metformin increases whole body cortisol generation by 11βHSD1 probably through
an indirect mechanism, potentially offsetting other metabolic benefits of
of Pycnogenol® as Add-on Drug to Metformin Therapy in Diabetic Rats -
Phytother Res. 2016 May 11 - "Pycnogenol® (PYC) belongs
to strong antioxidants that may interfere with different pathways playing an
important role in diseases associated with oxidative stress. Metformin (MET),
commonly used antidiabetic drug, has cardio-protective effects via activation of
AMP kinase (AMPK). In our study, we examined the effects of PYC as add-on drug
to metformin therapy in streptozotocin (STZ)-induced diabetic rats. Our results
revealed that both used agents, PYC and MET, showed improvement of blood glucose
levels, vascular reactivity, left ventricular hypertrophy, expression of AMPK,
glucose transporter 4 (GLUT4) and calcium/calmodulin-dependent protein kinase II
(CaMKII) in left ventricle of the hearts. However, the combination of these
interventions has failed to possess higher efficacy" - See
Pycnogenol at Amazon.com.
Has a Positive Therapeutic Effect on Prostate Cancer in Patients With Type 2
Diabetes Mellitus - Am J Med Sci. 2016 Apr;351(4):416-9 -
"Patients with prostate cancer along with DM2 who
remained on metformin were compared with controls who were not on metformin
matched by age, weight, race and Gleason score cancer staging ... There were
significantly fewer deaths (23% versus 10%), fewer recurrences (15% versus 8%),
fewer metastases (5% versus 0%) and fewer secondary cancers (17% versus 6%) in
the metformin group (P < 0.004). The final PSA value was lower in the
metformin-treated group with a result approaching significance" - See
metformin at IAS.
an Old Therapy that Deserves a New Indication for the Treatment of Obesity -
Curr Atheroscler Rep. 2016 Apr;18(4):16 - "Metformin is
not currently used for weight loss or diabetes prevention because it lacks an
FDA indication for obesity and/or pre-diabetes treatment. Based on the evidence,
metformin has been shown to decrease the incidence of type 2 diabetes, and
compares favorably to other weight-loss medications in terms of efficacy as well
as safety. Thus, metformin should be considered for a treatment indication in
patients with these conditions"
Activation by Nitrite and Metformin Improves Hyperglycemia and Normalizes
Pulmonary Hypertension Associated with Heart Failure with Preserved Ejection
Fraction (PH-HFpEF) - Circulation. 2016 Jan 26 -
"These studies validate a rodent model of metabolic syndrome and PH-HFpEF,
suggesting a potential role of nitrite and metformin as a preventative treatment
for this disease"
between Metformin Use and Mortality after Cervical Cancer in Older Women with
Diabetes - Cancer Epidemiol Biomarkers Prev. 2015 Dec 31 -
"Cumulative dose of metformin after cervical cancer
diagnosis was independently associated with a decreased risk of cervical
cancer-specific mortality and overall mortality in a dose-dependent fashion (HR
0.79 ... This finding has important implications if validated prospectively, as
metformin is inexpensive and can be easily combined with standard treatment for
and prostate cancer mortality: a meta-analysis - Cancer Causes Control. 2015
Nov 4 - "Metformin use was associated with improved
overall survival in studies with clear risk window definition (HR 0.88, 95 % CI
0.86-0.90, p < 0.001) and in studies with potential immortal time bias (HR 0.52,
95 % CI 0.41-0.65, p < 0.001). No significant association with prostate
cancer-specific mortality was detected (HR 0.76, 95 % CI 0.44-1.31, p = 0.33).
Metformin use was associated with a decreased risk of biochemical recurrence (HR
use and risk of colorectal adenoma after polypectomy in patients with type 2
diabetes mellitus - Cancer Epidemiol Biomarkers Prev. 2015 Sep 16 -
"Compared to patients not receiving diabetes medications
(n=1,578), metformin-only use (n=457) was associated with lower adenoma
recurrence risk (adjusted hazard ratio (HR)=0.76"
effects of metformin in combination with EGFR-TKI in treatment of patients with
advanced non-small cell lung cancer and type 2 diabetes - Cancer Lett. 2015
Sep 1 - "epidermal growth factor receptor (EGFR)
tyrosine kinase inhibitor (TKI) treatment ... Metformin use is associated with
improved survival and delayed onset of acquired resistance to EGFR-TKI"
metformin on breast ductal carcinoma in situ proliferation in a randomized
pre-surgical trial - Cancer Prev Res (Phila). 2015 Aug 14 -
"Metformin is associated with lower breast cancer (BCa)
risk in epidemiological studies and showed decreased proliferation in
HER2-positive BCa in a pre-surgical trial ... We randomly assigned 200
non-diabetic patients diagnosed with invasive BCa in core biopsies to metformin,
1700 mg or placebo once daily for 28 days prior to surgery ... In tissue samples
obtained following 4 weeks of study drug, proliferation was lower in
HER2-positive DCIS for women randomized to metformin vs. placebo"
With Metformin Improves Erectile Dysfunction in a Murine Model of Obesity
Associated With Insulin Resistance - Urology. 2015 Jul 18 -
"Treatment with metformin restored the erectile function
in obese mice, through improvement of in vitro endothelial and nitrergic
cavernosal relaxations. Therefore, use of metformin may be a good pharmacologic
approach to treat insulin resistance-associated erectile dysfunction"
inhibits age-related centrosome amplification in Drosophila midgut stem cells
through AKT/TOR pathway - Mech Ageing Dev. 2015 May 16 -
"Age-related changes in tissue-resident stem cells may
be closely associated with tissue aging and age-related diseases, such as
cancer. Centrosome amplification is a hallmark of cancers ... metformin, a
recognized anti-cancer drug, inhibits age- and oxidative stress-induced
centrosome amplification in ISCs ... Our study reveals the beneficial and
protective effects of metformin on centrosome amplification via AKT/TOR
improves putative longevity effectors in peripheral mononuclear cells from
subjects with prediabetes. A randomized controlled trial - Nutr Metab
Cardiovasc Dis. 2015 Mar 24 - "Compared to baseline,
metformin significantly improved metabolic parameters and insulin sensitivity,
increased SIRT1 gene/protein expression and SIRT1 promoter chromatin
accessibility, elevated mTOR gene expression with concomitant reduction in
p70S6K phosphorylation in subjects' PBMCs, and modified the plasma N-glycan
profile. Compared to placebo, metformin increased SIRT1 protein expression and
reduced p70S6K phosphorylation (a proxy of mTOR activity). Plasma N-glycans were
also favourably modified by metformin compared to placebo"
inhibits the proliferation of human prostate cancer PC-3 cells via the
downregulation of insulin-like growth factor 1 receptor - Biochem Biophys
Res Commun. 2015 Apr 7 - "Recent studies have shown that
metformin inhibits cancer cell proliferation and tumor growth both in vitro and
in vivo ... Our results suggest that metformin is a potent inhibitor of the
IGF-1/IGF-1R system and may be beneficial in prostate cancer treatment"
amplifies the effects of metformin on insulin sensitivity and glycemic control
in diet-induced obese mice - Metabolism. 2015 Mar 19 -
"These data demonstrate that adding Leu to Met enables a
dose reduction of 66% with improved efficacy and of 83% with comparable efficacy
to standard metformin in diet-induced obese mice" - See
leucine products at Amazon.com.
metformin and aspirin on life history features and longevity of crickets:
trade-offs versus cost-free life extension? - Age (Dordr). 2015
Apr;37(2):9769 - "Both drugs significantly increased
survivorship and maximal life span. Maximal longevity was 136 days for controls,
188 days (138 % of controls) for metformin, and 194 days (143 % of controls) for
aspirin. Metformin and aspirin in combination extended longevity to a lesser
degree (163 days, 120 % of controls)"
reduces ovarian cancer risk in Taiwanese women with type 2 diabetes mellitus
- Diabetes Metab Res Rev. 2015 Mar 28 - "The overall
fully adjusted hazard ratio (95% confidence intervals) for ever- versus
never-users was 0.658 (0.593-0.730). The fully adjusted hazard ratios for the
first, second, and third tertiles of cumulative duration of metformin therapy
were 1.169 (1.019-1.341), 0.761 (0.644-0.898) and 0.276 (0.225-0.340),
respectively (P-trend <0.01); and 1.220 (1.067-1.395), 0.610 (0.513-0.725) and
0.305 (0.248-0.374), respectively (P-trend <0.01), for cumulative dose of
Immune-mediated antitumor effect by type 2 diabetes drug, metformin - Proc
Natl Acad Sci U S A. 2015 Jan 26 - "Metformin, a
prescribed drug for type 2 diabetes, has been reported to have anti-cancer
effects; however, the underlying mechanism is poorly understood. Here we show
that this mechanism may be immune-mediated. Metformin enabled normal but not
T-cell-deficient SCID mice to reject solid tumors. In addition, it increased the
number of CD8+ tumor-infiltrating lymphocytes (TILs) and protected them from
apoptosis and exhaustion characterized by decreased production of IL-2, TNFα,
and IFNγ. CD8+ TILs capable of producing multiple cytokines were mainly
PD-1-Tim-3+, an effector memory subset responsible for tumor rejection"
Metformin on Energy Intake and Satiety in Obese Children - Diabetes Obes
Metab. 2014 Dec 8 - "Compared with placebo, metformin
treatment elicited significant reductions from baseline in adjusted mean energy
intake after the pre-meal load (metformin: -104.7 ± 83.8 kcal vs. placebo:
+144.2 ± 96.9 kcal; p = 0.034) independent of changes in body composition.
Metformin also significantly decreased ratings of hunger (-1.5 ± 5.6 vs.
+18.6 ± 6.3; p = 0.013) and increased ratings of fullness (+10.1 ± 6.2 vs.
-12.8 ± 7.0; p = 0.01) following the pre-meal load"
of vitamin D3 and metformin exhibits synergistic chemopreventive effects on
colorectal neoplasia in rats and mice - Cancer Prev Res (Phila). 2014 Nov 21
- "These findings show that combined use of vitamin D3
and metformin exhibits synergistic effects against the development of early
colon neoplasia. They suggest that the combined use of vitamin D3 and metformin
may represent a novel strategy for chemoprevention of colorectal cancer"
metformin at IAS and
vitamin D at Amazon.com.
metformin therapy and dietary supplements on semen parameters in
hyperinsulinaemic males - Andrologia. 2014 Oct 30 -
"Nineteen hyperinsulinaemic male patients were treated for 3 months with
metformin alone (Group A), and fifteen patients used metformin in combination
with the nutritional supplement (Group B) ... The improvement in sperm
morphology after treatment was similar for the two respective groups (P < 0.05).
The morphological normal sperm forms increased from the mean percentage of 3.9
to 5.5% and from 4.2 to 5.5% for Group A and B respectively. Where a combination
of metformin and the supplement were used (Group B), the combination treatment
proved to be superior in obtaining enhanced chromatin packaging quality although
not statistically significant (P = 0.5929) when compared with the metformin
(Group A) group. The chromatin packaging quality in Group B improved with 10%
while the improvement in Group A was approximately 8.3%"
drug metformin is effective on the metabolism of asymmetric dimethylarginine in
experimental liver injury - Diabetes Res Clin Pract. 2014 Sep 16 -
"Our findings showed that metformin administration for
one week has a potency to protect liver through regulating ADMA metabolism in
upregulated by metformin inhibits the function of androgen receptor in prostate
cancer cells - Cancer Lett. 2014 Sep 5 - "Metformin,
a diabetes drug, has been reported to inhibit the growth of prostate cancer
cells ... metformin upregulated the protein level of small heterodimer
partner-interacting leucine zipper (SMILE), a coregulator of nuclear receptors,
and knockdown of SMILE expression with shRNA abolished the inhibitory effect of
metformin on AR function ... these results suggest that SMILE, which is induced
by metformin, functions as a novel AR corepressor and may mediate the inhibitory
effect of metformin on androgen-dependent growth of prostate cancer cells"
Inhibits Epithelial-Mesenchymal Transition in Prostate Cancer Cells: Involvement
of the Tumor Suppressor miR30a and its Target Gene SOX4 - Biochem Biophys
Res Commun. 2014 Sep 5 - "Tumor metastasis is the
leading cause of mortality and morbidity of prostate cancer (PCa) patients.
Epithelial-mesenchymal transition (EMT) plays a critical role in cancer
progression and metastasis. Recent evidence suggested that diabetic patients
treated with metformin have lower PCa risk and better prognosis ... metformin
significantly inhibits proliferation of Vcap and PC-3 cells, induces G0/G1 cell
cycle arrest and inhibits invasiveness and motility capacity of Vcap cells"
associated with reduced risk of pancreatic cancer in patients with type 2
diabetes mellitus: A systematic review and meta-analysis - Diabetes Res Clin
Pract. 2014 Apr 18 - "Use of metformin was associated
with a significant lower risk of pancreatic cancer [RR 0.63"
prognostic value of metformin for cancer patients with concurrent diabetes- a
systematic review and meta-analysis - Diabetes Obes Metab. 2014 Jan 27 -
"A literature search was performed using the PubMed,
EMbase and SciVerse Scopus databases ... metformin was associated with lower
risk of all-cause mortality in cancer patients with concurrent diabetes,
particularly for breast (pooled relative risk (RR) 0.70, 95% CI 0.55, 0.88;
P=0.003), colorectal (RR 0.70, 95% CI 0.59, 0.84; P<0.001), ovarian (RR 0.44,
95% CI 0.30, 0.64; P<0.001) and endometrial cancer (RR 0.49, 95% CI 0.32, 0.73;
P=0.001). In addition, metformin was associated with lower risks of
metabolic disruptor and anti-diabetic drug to target human leukemia - Cancer
Lett. 2014 Jan 21 - "We present here how metformin, an
anti-diabetic drug that has attracted a strong interest for its recently
discovered anti-cancer properties, can be envisioned as a new adjuvant approach
to treat leukemia. Metformin may have a double-edged sword effect i) by acting
on the organism to decrease hyperglycaemia and hyperinsulinemia in diabetic
patients and ii) at the cellular level, by inhibiting the mTORC1-cancer
supporting pathway through AMPK-dependent and independent mechanisms"
Protects Against Systolic Overload-Induced Heart Failure Independent of
AMP-Activated Protein Kinase α2 - Hypertension. 2014 Jan 13 -
"metformin protects against adverse remodeling through a
pathway that seems independent of AMPKα2"
relationship between metformin therapy and sleep quantity and quality in
patients with Type 2 diabetes referred for potential sleep disorders -
Diabet Med. 2013 Nov 16 - "Given that sleep disorders
are known to be related to insulin resistance, and metformin has favourable
effects on insulin resistance and on ventilatory drive, we sought to determine
whether metformin therapy was related to sleep variables in a group of patients
with Type 2 diabetes ... Total sleep time and sleep efficiency were higher in
metformin-treated patients than in patients not treated with metformin [total
sleep time: 6 h 39 min vs. 6 h 3 min, respectively (P = 0.002); sleep
efficiency: 77.9 +/- 12.3 vs. 71.5 +/- 17.2%, respectively"
Inhibits Skin Tumor Promotion in Overweight and Obese Mice - Cancer Prev Res
(Phila). 2013 Nov 6 - "Collectively, the current data
demonstrate that metformin given in the drinking water effectively inhibited
skin tumor promotion in both overweight and obese mice"
Anti-Diabetic Medications and the Risk of Colorectal Cancer in Patients with
Diabetes Mellitus: A Systematic Review and Meta-Analysis - Cancer Epidemiol
Biomarkers Prev. 2013 Sep 16 - "Meta-analysis of
observational studies showed an 11% reduction in CRC risk associated with
metformin use (n=9 studies; OR, 0.89; 95% CI, 0.81-0.99), whereas TZD use was
not associated with CRC risk (n=5 studies; OR, 0.96; 95% CI, 0.87-1.05).
Conversely, a trend towards higher CRC risk was observed with sulfonylurea (n=7
studies; OR, 1.11; 95% CI, 0.97-1.26) and insulin (n=9 studies; OR, 1.33; 95%
CI, 0.91-1.94) use, although these associations were not statistically
Relationship between metformin use, vitamin B12 deficiency,
hyperhomocysteinemia and vascular complications in patients with type 2
diabetes - Endocr J. 2013 Sep 8 -
"Metformin-induced B12 lowering in diabetes was associated with elevation of
homocysteine, and hyperhomocysteinemia was independently related to
retinopathy" - See
vitamin B12 at Amazon.com.
Increased Risk of Cognitive Impairment in Patients With Diabetes Is
Associated With Metformin - Diabetes Care. 2013 Sep 5 -
"Metformin use was associated with impaired
cognitive performance. Vitamin B12 and calcium supplements may alleviate
metformin-induced vitamin B12 deficiency and were associated with better
cognitive outcomes" - See
vitamin B12 at Amazon.com.
of Metformin Dose on Cancer Risk Reduction in Patients with Type 2 Diabetes
Mellitus: A 6-Year Follow-up Study - Pharmacotherapy. 2013 Jul 17 -
"Longitudinal Health Insurance Database ... A total
of 65,754 age- and gender-matched patients without diabetes and no previous
cancer diagnosis were extracted from the database ... Our results revealed
dose-dependent effects of metformin on cancer risk and cancer onset times. A
significant decrease in cancer risk was found in the monotherapy group who
received more than 360 defined daily doses (DDDs) of metformin (hazard ratio
[HR] 0.40, 95% confidence interval [CI] 0.24-0.66). The greatest decrease in
cancer risk was observed in patients who took more than 1080 DDDs (HR 0.27,
95% CI 0.09-0.84). Significantly greater dose-dependent effects were seen in
patients who used metformin in combination with other antidiabetic drugs"
metformin at IAS.
Association Between Metformin Use and Risk of Prostate Cancer and Its Grade
- J Natl Cancer Inst. 2013 Jul 13 - "There was no
association between metformin use and risk of any prostate cancer (aOR =
1.03, 95% confidence interval [CI] = 0.96 to 1.1), high-grade cancer (aOR =
1.13, 95% CI = 0.96 to 1.32), low-grade cancer (aOR = 0.94, 95% CI = 0.82 to
1.06), or biopsy-diagnosed cancer (aOR = 0.98, 95% CI = 0.84 to 1.02)"
Metformin for Weight Loss and Metabolic Control in Overweight Outpatients
With Schizophrenia and Schizoaffective Disorder - Am J Psychiatry. 2013
Jul 12 - "Metformin was titrated up to 1,000 mg
twice daily, as tolerated ... Mean change in body weight was -3.0 kg (95%
CI=-4.0 to -2.0) for the metformin group and -1.0 kg (95% CI=-2.0 to 0.0)
for the placebo group, with a between-group difference of -2.0 kg (95%
CI=-3.4 to -0.6). Metformin also demonstrated a significant between-group
advantage for BMI (-0.7; 95% CI=-1.1 to -0.2), triglyceride level (-20.2
mg/dL; 95% CI=-39.2 to -1.3), and hemoglobin A1c level (-0.07%; 95% CI=-0.14
to -0.004). Metformin-associated side effects were mostly gastrointestinal
and generally transient, and they rarely led to treatment discontinuation"
- Note: 3 kg is 6.6 pounds.
study of metformin exposure and survival in patients with stage I-III
colorectal cancer - Cancer Epidemiol Biomarkers Prev. 2013 Jun 10 -
"Adult stage I-III colorectal cancer patients
diagnosed 2001-2006 were identified from the National Cancer Registry
Ireland. Use of metformin and other anti-diabetic medications was determined
from a linked national prescription claims database ... High intensity
exclusive metformin use was associated with a significant reduction in
colorectal cancer-specific mortality (HR 0.44"
Treatment with Metformin is Associated with Higher Remission Rate in
Diabetic Patients with Thyroid Cancer - J Clin Endocrinol Metab. 2013
May 24 - "complete response (CR) ... progression
free survival (PFS) ... Tumor size is smaller in patients treated with
metformin suggesting inhibition of tumor growth by the drug. Among
diabetics, absence of metformin therapy is an independent factor for
decreased likelihood of CR and increased risk of shorter PFS"
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
of Pioglitazone Versus Metformin on Cardiovascular Risk Markers in Type 2
Diabetes - Adv Ther. 2013 Jan 22 - "The primary
objective of this study was to evaluate the effect on C-reactive protein
(CRP) after a 16-week treatment period with either pioglitazone or metformin
... Pioglitazone treated patients were found to have statistically
significantly larger decreases in mean CRP levels (-0.4 mg/dL) compared to
those treated with metformin (-0.2 mg/dL) (P = 0.04), as well as greater
reductions in levels of mean fasting plasma glucose (-27 vs. -9 mg/dL; P =
0.01), serum insulin (-2 vs. -1.9 mU/L; P = 0.014), homeostatic model
assessment (HOMA) (-1.2 vs. -0.9; P = 0.015), and E-selectin (-12.4 vs. +3.4
μg/mL; P = 0.01). Mean glycated hemoglobin (HbA(1c)) levels decreased in
both treatment groups from baseline to week 16 (-0.4% in the pioglitazone
group, -0.2% in the metformin group; P = 0.36). Pioglitazone treatment was
also found to be associated with a statistically significant increase in
total cholesterol levels (+10 mg/dL in the pioglitazone arm, -3 mg/dL in the
metformin arm; P = 0.05) and a decrease in liver enzyme levels"
Metformin and Prostate
Cancer: Reduced Development of Castration-resistant Disease and Prostate Cancer
Mortality - Eur Urol. 2012 Dec 14 -
"castration-resistant prostate cancer (CRPC) ... prostate-specific
antigen-recurrence-free survival (PSA-RFS), distant metastases-free survival
(DMFS), prostate cancer-specific mortality (PCSM), overall survival (OS) ...
With a median follow-up of 8.7 yr, the 10-yr actuarial rates for metformin,
diabetic non-metformin, and nondiabetic patients for PCSM were 2.7%, 21.9%, and
8.2% (log-rank p ≤ 0.001), respectively. Metformin use independently predicted
(correcting for PSA, T stage, Gleason score, age, diabetic status, and
androgen-deprivation therapy use) improvement in all outcomes compared with the
diabetic non-metformin group; PSA-RFS (hazard ratio [HR]: 1.99 [1.24-3.18];
p=0.004), DMFS (adjusted HR: 3.68 [1.78-7.62]; p<0.001), and PCSM (HR: 5.15
[1.53-17.35]; p=0.008). Metformin use was also independently associated with a
decrease in the development of CRPC in patients experiencing biochemical failure
compared with diabetic non-metformin patients (odds ratio: 14.81 [1.83-119.89];
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.
- 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
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"
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"
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)"
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"
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
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
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"
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
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)"
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"
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"
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
"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
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"
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"
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"
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"
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)"
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)"
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"
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"
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"
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"
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
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"
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)"
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"
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
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
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"
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"
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"
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
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
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
statins and fibrates, or
enzyme inhibitors and
angiotensin II receptor blockers are the first-line lipid-modifying or
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
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
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
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 IAS.
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
"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
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
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
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
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
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