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Recent Longevity News for the seven days ending
5/22/13. You should consult your doctor if you are taking any medications.
Mediterranean diet seems to boost aging brain power - Science Daily, 5/21/13
- "Participants, who were all taking part in the
PREDIMED trial looking at how best to ward off cardiovascular disease, were
randomly allocated to a Mediterranean diet
with added olive oil or mixed nuts or a control group receiving advice to follow
the low-fat diet typically recommended to prevent heart attack and stroke ...
After an average of 6.5 years, they were tested for signs of
cognitive decline using a Mini Mental State Exam
and a clock drawing test ... The average scores on both tests were significantly
higher for those following either of the Mediterranean diets compared with those
on the low fat option"
steroids may affect future mental health - Science Daily, 5/20/13 -
"The study included almost 700 former Swedish wrestlers,
weightlifters, powerlifters and throwers who competed at the elite level
sometime between 1960 and 1979 ... We found a clear link.
AAS users were more likely to have been
treated for depression, concentration problems and aggressive behaviour"
Extra Vitamin D May Ease Crohn's Symptoms, Study Finds - WebMD, 5/20/13 -
"Extra vitamin D "was
associated with significantly less physical, emotional and general fatigue,
greater quality of life and the ability to perform activities of daily living,"
... evaluated 27 patients who had Crohn's in
remission. (Even in remission, fatigue and quality of life can be problematic.)
The patients were assigned to take either 2,000 IUs (international units) of
vitamin D a day or a dummy vitamin for three months" - See
vitamin D at Amazon.com.
Sugar-sweetened beverages associated with increased kidney stone risk -
Science Daily, 5/15/13 - "Twenty percent of American
males and 10 percent of American females will experience a
kidney stone at some point in their
lifetime ... They found that participants who consumed one or more
sugar-sweetened cola servings per day had a 23 percent higher risk of developing
kidney stones compared with those participants consuming less than one serving
per week. This was true for consuming sugar-sweetened non cola as well, such as
punch. They also found that some beverages, such as coffee, tea and orange
juice, were associated with a lower risk of stone formation"
Dietary Intake of Saturated
Fatty Acids and Incident Stroke - Medscape, 5/15/13 -
"We sought to test the hypothesis that
SFA intake is associated inversely with
risk of stroke and its subtypes and positively
with coronary heart disease among Japanese, whose average SFA intake is lower
than that of Westerners ... We found inverse associations between SFA intake and
total stroke [multivariable hazard ratio (95% confidence interval) for the
highest vs. lowest quintiles = 0.77 (0.65–0.93), trend P = 0.002],
intraparenchymal haemorrhage [0.61 (0.43–0.86), P for trend = 0.005], and
ischaemic stroke [0.84 (0.67–1.06), trend P = 0.08], primarily for deep
intraparenchymal haemorrhage [0.67 (0.45–0.99), P for trend = 0.04] and lacunar
infarction [0.75 (0.53, 1.07), trend P = 0.02]. We also observed a positive
association between SFAs intake and myocardial infarction [1.39 (0.93–2.08),
trend P = 0.046] primarily among men. No associations were observed between SFAs
intake and incidence of subarachnoid haemorrhage or sudden cardiac death"
- Note: So maybe moderation is the key.
may stall effects of junk food on brain - Science Daily, 5/14/13 -
"high-fat diets could disrupt neurogenesis, a process
that generates new nerve cells, but diets rich in omega-3s could prevent these
negative effects by stimulating the area of the brain that control feeding,
learning and memory ... Excessive intake of certain macronutrients, the refined
sugars and saturated fats found in junk food, can lead to weight gain, disrupt
metabolism and even affect mental processing ... These changes can be seen in
the brain's structure, including its ability to generate new nerve cells,
potentially linking obesity to neurodegenerative diseases ...
omega-3 fish oils can reverse or even prevent
these effects ... omega-3s restore normal function by interfering with the
production of these inflammatory molecules, suppressing triglycerides, and
returning these nerve growth factors to normal ... Fish oils don't appear to
have a direct impact on weight loss, but they may take the brakes off the
detrimental effects of some of the processes triggered in the brain by high-fat
diets. They seem to mimic the effects of calorie restrictive diets and including
more oily fish or fish oil supplements in our diets could certainly be a
positive step forward for those wanting to improve their general health"
Mega Twin EPA at Amazon.com
Jarrow Max DHA at Amazon.com.
No Benefit in Sharply Restricting Salt, Panel Finds - New York Times,
5/14/13 - "But the new expert committee, commissioned by
the Institute of Medicine at the behest of the Centers for Disease Control and
Prevention, said there was no rationale for anyone to aim for
sodium levels below 2,300 milligrams a day ...
One 2008 study the committee examined, for example, randomly assigned 232
Italian patients with aggressively treated moderate to severe congestive heart
failure to consume either 2,760 or 1,840 milligrams of sodium a day, but
otherwise to consume the same diet. Those consuming the lower level of sodium
had more than three times the number of hospital readmissions — 30 as compared
with 9 in the higher-salt group — and a more than twice as many deaths — 15 as
compared with 6 in the higher-salt group ... Another study ... the risks of
heart attacks, strokes, congestive heart failure and death from heart disease
increased significantly for those consuming more than 7,000 milligrams of sodium
a day and for those consuming less than 3,000 milligrams of sodium a day"
Abstracts from this week's
Doctor's Guide Nutrition/Dietetics
plus abstracts from my RSS feeds (Click here
for the journals, the PubMed ones at the top):
improves learning and memory in normally aged mice through microRNA-CREB pathway
- Biochem Biophys Res Commun. 2013 May 15 - "Here we
report that, after intraventricular injection of
RSV for one week in 8-9 month-old mice, the long-term
memory formation and the LTP induction from
hippocampus CA1 were improved ... These findings demonstrate a role for RSV in
cognition and a microRNA-CREB-BDNF mechanism by which RSV regulates these
processes, demonstrating its value as a potential therapeutic target against CNS
disorders in aging" - See
resveratrol products at Amazon.com.
calcium, vitamin D, and dairy servings and dental plaque in older Danish adults
- Nutr J. 2013 May 16;12(1):61 - "Intakes of calcium
dairy-servings within-recommendations were inversely associated with
plaque, among those with higher, but not lower,
vitamin D intakes. Due to the cross-sectional
nature of the study, it is not possible to infer that this association is
causal" - See
vitamin D at Amazon.com.
delivery affect postnatal coitus? - Int J Impot Res. 2013 May 16 -
"We concluded that vaginal delivery indeed may result in
loose vagina compared with cesarean delivery. However, it did not negatively
affect the postnatal sexual function.
Therefore, women should be assured that their sexual functions won't be affected
by the types of delivery"
serum folate status on total folate and 5-methyltetrahydrofolate in human skin
- Am J Clin Nutr. 2013 May 15 - "Total
folate (by using a microbiological assay) and
5-MTHF (by using high-pressure liquid chromatography) were measured in fasting
serum and fresh skin obtained at surgery by using a recovery validated
extraction method ... The high proportion of 5-MTHF in the epidermis, which is
further emphasized in subjects with a lower (10-20-nM) serum folate status,
points to a special role for this form of folate in skin, perhaps as a
protectant from ultraviolet-induced photosensitization reactions. 5-MTHF may
also maintain methylation reactions that influence the proliferative activity.
These results may help to individualize the treatment of psoriasis patients with
methotrexate and folate" - See
folic acid products at Amazon.com.
consumption in relation to risk of cardiovascular disease and diabetes: a
systematic review and meta-analysis - Am J Clin Nutr. 2013 May 15 -
"A systematic literature review was conducted for
published studies in PubMed and EMBASE through March 2012 ... This meta-analysis
is not associated with the risk of CVD and cardiac mortality in the general
population. However, egg consumption may be associated with an increased
incidence of type 2 diabetes among the general population and CVD comorbidity
among diabetic patients" - Note: Unless they can figure out a way
to filter out how people are cooking those eggs and what they are eating with
the eggs, I don't see how the study is useful. Just think how frying the
eggs, eating bacon, sausage, ham, fried hash browns and toast with margarine
(hydrogenated oils) or butter can skew the study over just eggs cooked in a
microwave with cooking spray.
- Here's what I use sprayed with olive oil. The secret is that you have
to turn it over. I go 50 seconds on one side and 42 seconds on the other.
Don't wait in-between.
Chef Buddy Microwave Egg Cooker
Misto Tritan Oval Oil Sprayer Bottle, White
levels of 25-hydroxyvitamin D predict hip fracture in the elderly. A NOREPOS
study - J Clin Endocrinol Metab. 2013 May 15 - "risk
of hip fracture in Norway, a high-latitude country that has among the highest
hip fracture rates worldwide ... We observed an inverse association between
hip fracture; those with s-25(OH)D in the
lowest quartile (<42.2 nmol/l) had a 38% (95% CI 9-74%) increased risk of hip
fracture compared with the highest quartile ... In this prospective case-cohort
study of hip fractures, the largest ever reported, we found an increased risk of
hip fracture in subjects in the lowest compared to the highest quartile of serum
25-hydroxyvitamin D" - See
vitamin D at Amazon.com.
Protein, Lipid-soluble Micronutrients, and Survival in Colorectal Cancer
Patients - Cancer Epidemiol Biomarkers Prev. 2013 May 15 -
"A positive association with overall risk of death was
observed for CRP (HR for highest vs.
lowest quintile: 1.80; 95% CI: 1.07-3.04; Ptrend=0.01) whereas, inverse
associations were generally observed for retinol
and carotenoids (HRs for overall risk of
death for the highest quintile ranging from 0.5-0.8) ... These observations are
consistent with a direct relationship between circulating CRP and overall
survival among colorectal cancer patients ...
These results, if reproduced, suggest that reduction of inflammation should be
explored as a potential complementary treatment strategy"
content in hepatic and gonadal adipose tissue parallel aortic cholesterol
accumulation in mice fed diets with different omega-6 PUFA to EPA plus DHA
ratios - Clin Nutr. 2013 Apr 24 - "Dietary
ratios did not affect body weight, but lower ω-6:EPA+DHA ratio diets decreased
liver lipid accumulation, which possibly contributed to the lower aortic
cholesterol accumulation" -
Mega Twin EPA at Amazon.com
Jarrow Max DHA at Amazon.com.
Control and Risk of Cardiovascular Disease Hospitalization and All-Cause
Mortality - J Am Coll Cardiol. 2013 May - "Compared
with patients with mean A1C 7.0%-7.4%, those with
mean A1C <6.0% had a 75% increased risk of CVD hospitalization (hazard ratio
[HR] 1.68, 95% CI 1.39-2.04, p<0.001) after adjustment for demographic and
clinical characteristics. Those with A1C 6.0%-6.4% (1.18, 1.00-1.40, p=0.048)
and 6.5%-6.9% (1.18, 1.02-1.37, p=0.031) also had significantly higher risk
relative to the reference group of 7.0%-7.4%, as did patients with A1C 8.5%-8.9%
(HR 1.55, 1.24-1.94, p<0.001) and >9.0% (HR 1.83, 1.50-2.22, p<0.001). Risk of
all-cause mortality was significantly greater than the reference group among A1C
categories <6.0%, 6.0%-6.4%, 6.5%-6.9%, and >9.0% ... The relationship between
mean A1C and CVD hospitalizations and all-cause mortality is U-shaped, with
greater risk at both higher and lower A1C levels"
Neat Tech Stuff / "How To's":
Health Focus (Metformin):
Where to purchase Metformin (don't take unless under a
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
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
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"
- Pioglitazone and
Metformin Similarly Effective in Reducing HbA1c - Medscape, 12/13/04
Research Highlights Hormonal Control of Cardiovascular Functions -
Doctor's Guide, 8/17/04 -
"The Patients who received metformin experienced an
improvement in several endothelial function markers, including weight,
fasting plasma glucose, soluble intercellular adhesion molecule and soluble
vascular cell adhesion molecule"
Metformin Shows Promise for Diabetes Prevention, but Further Studies Needed
- Doctor's Guide, 6/24/04 -
"After 1 year of treatment, patients receiving
metformin experienced a significantly lower increase in fasting blood
glucose levels compared with the placebo group (3.6 mg/dL vs. 7.2 mg/dL, P <
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
Metformin May Improve Cardiac Autonomic System Balance in Overweight
Patients with Type 2 Diabetes - Doctor's Guide, 3/15/04
Metformin Improves Metabolic Control and Other Physiologic Variables in Type
2 Diabetes - Doctor's Guide, 2/25/04
What You Don’t Know About Blood Sugar - Life Extension Magazine, 1/04 -
"it now appears that optimal fasting blood glucose
levels should probably be under 86 mg/dL ...
Chromium supplements have been shown to
reduce blood glucose significantly.70-74 The dose used in human studies
ranges from 200 to 1000 mcg of elemental chromium a day, with best results
occurring when 400 mcg or more of chromium is taken daily ... Nondiabetics
using metformin may start off at 500 mg a day and gradually build up to
1000-1500 mg a day. The objective is not to take so much metformin as to
induce a hypoglycemic state" - See
iHerb chromium products.
Metformin and Carbohydrate-Modified Diet May Help Sustain Weight Loss -
Doctor's Guide, 12/16/03
No Apparent Increased Risk of Lactic Acidosis Found In Type 2 Diabetics Who
Take Metformin - Doctor's Guide, 11/25/03
Metformin May Improve Metabolic Control in Adolescents with Type I Diabetes
- Doctor's Guide, 11/21/03
Metformin Decreases Serum C-Reactive Protein in Women With Polycystic
Ovarian Syndrome - Doctor's Guide, 10/28/03
Metformin Seems to be Effective for Anovulation in Women with Polycystic
Ovary Syndrome - Doctor's Guide, 10/27/03
Metformin Treatment Leads to Increased Homocysteine, Decreased Vitamin B12
and Folate in Type 2 Diabetes Patients - Doctor's Guide, 10/20/03 -
"Homocysteine requires folate and vitamin B12 to be
properly metabolised, and serum vitamin B12 levels are known to decrease
during metformin treatment ... compared with placebo, metformin was
associated with an increase in serum homocysteine levels (4% [0.2 to 8 µmol
L-1]; P=0.039), and decreases in vitamin B12 (-14% [-4.2 to -24 pmol L-1];
P<0.0001) and folate (-7%"
Uses of Metformin May Extend Beyond Patients with Type 2 Diabetes -
Doctor's Guide, 9/4/03 -
"In type 2 diabetics, metformin appears to decrease
plasma fasting glucose and HbA1c levels without
causing weight gain. Metformin may also have a positive influence on a
variety of cardiovascular risk factors and may be useful in preventing
diabetes in overweight individuals with
mild hyperglycaemia ... while further study is necessary before more
widespread use is encouraged, the role of metformin may be expanded for
glucose control in children and teenagers with type 2 diabetes, in
non-diabetic women with PCOS, and to prevent progression to diabetes"
FDA Approves New Avandamet (Rosiglitazone Maleate/Metformin) Dosage
Strengths For Treatment Of Type 2 Diabetes - Doctor's Guide, 8/27/03
Lifestyle Modification, Metformin Effective Prevention for Type 2 Diabetes
- Doctor's Guide, 7/31/03 -
"1,073 patients were prescribed 850 mg metformin
twice daily, 1,082 had placebo twice daily, and 1,079 were prescribed an
intensive program of lifestyle modification ... Incidence of
diabetes was 58% lower ... in the lifestyle
intervention group and 31% lower ... in the metformin group than in the
Inappropriate Metformin Use Frequent in Hospitalised Patients - Doctor's
BioMarker Pharmaceuticals Develops Anti-Aging Therapy - LE Magazine
cover story, 6/03 -
"The BioMarker scientists found that all the
glucoregulatory agents reproduced some of the gene expression effects of CR
[calorie restriction], but that metformin
was the undisputed star of the group, being twice as effective as the others
in reproducing the effects of CR"
Pioglitazone/Sulfonylurea And Pioglitazone/Metaformin Combinations Both
Effective For Reducing Very Low Density Lipoproteins And Free Fatty Acids
- Doctor's Guide, 5/21/03
Repaglinide + Metformin Superior to Nateglinide + Metformin in Treating Type
2 Diabetes - Doctor's Guide, 5/18/03
Benfluorex Improves Glycaemic Control In Type 2 Diabetes - Doctor's
Guide, 4/29/03 -
"Although benfluorex may be less potent than
metformin, it lowers haemoglobin A1C (HbA1C) and fasting plasma glucose
levels and is well tolerated"
Metformin-Glibenclamide Combination Is More Effective Than Monotherapy In
Type 2 Diabetes - Doctor's Guide, 4/24/03
Pioglitazone Improves Insulin Sensitivity Compared To Metformin -
Doctor's Guide, 4/22/03
Combination Therapy Improves Management of Obese Diabetics - Doctor's
Guide, 4/15/03 -
insulin-sensitising thiazolidinedione drug, to metformin, a biguanide agent,
greatly enhances the management of obese type 2
diabetic patients who are
inadequately controlled by metformin alone"
Metformin Concentrations In Erythrocytes Have Clinical Implications -
Doctor's Guide, 3/25/03
Diabetes Prevention Efforts Achieving Good Results - Doctor's Guide,
"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 reductions"
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" - See
Metformin and Prostate
Cancer: Reduced Development of Castration-resistant Disease and Prostate Cancer
Mortality - Eur Urol. 2012 Dec 14 -
"castration-resistant prostate cancer (CRPC) ... prostate-specific
antigen-recurrence-free survival (PSA-RFS), distant metastases-free survival
(DMFS), prostate cancer-specific mortality (PCSM), overall survival (OS) ...
With a median follow-up of 8.7 yr, the 10-yr actuarial rates for metformin,
diabetic non-metformin, and nondiabetic patients for PCSM were 2.7%, 21.9%, and
8.2% (log-rank p ≤ 0.001), respectively. Metformin use independently predicted
(correcting for PSA, T stage, Gleason score, age, diabetic status, and
androgen-deprivation therapy use) improvement in all outcomes compared with the
diabetic non-metformin group; PSA-RFS (hazard ratio [HR]: 1.99 [1.24-3.18];
p=0.004), DMFS (adjusted HR: 3.68 [1.78-7.62]; p<0.001), and PCSM (HR: 5.15
[1.53-17.35]; p=0.008). Metformin use was also independently associated with a
decrease in the development of CRPC in patients experiencing biochemical failure
compared with diabetic non-metformin patients (odds ratio: 14.81 [1.83-119.89];
p=0.01)" - See
metformin at IAS.
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
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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