3.3.1 Effect of metformin in cancer
To further investigate the anti-aging benefits of metformin seen in
animal models, numerous studies have been conducted to replicate these
results in humans 89. In 2005, a case-control study
first suggested that the use of metformin in diabetic patients was
associated with reduced risk of cancer 91. Since then,
the anti-tumor effect of metformin has been extensively investigated in
multiple observational studies. In particular, Libby et al. and his
colleagues compared new users of metformin and those who were taking
sulfonylurea, insulin, or other anti-diabetic drugs. Their results
showed that in patients with T2DM, metformin users (n= 4,085) have a
significant lower risk of cancer than non-users (n= 4,085 ) do after
adjusting for covariates (Hazard Ratio [HR] 0.63, 95% Confidence
Interval [CI] [0.53-0.75]) 92.
Although a large body of subsequent observational studies have supported
the positive relationship between metformin use and its anti-cancer
effect, the evidence from Randomized Control Trials (RCTs) has been
largely inconclusive 93, 94. For instance, Home and
his colleagues compared the malignancy rates among diabetic patients who
were initially treated with different glucose lowering medications.
Their results did not support the view that metformin had a protective
effect against cancer compared with rosiglitazone and sulfonylureas95. Consistently, multiple meta-analysis did not find
any evidence showing metformin treatment being associated with a
reduction of cancer incidence 96, 97.
Taken together, metformin use in animal studies and some observational
studies have indicated its great potential as a cancer protective agent,
which has sparked great interest for expansion to human clinical trials.
Encouragingly, multiple RCTs that aim to investigate the anti-aging
properties of metformin in non-diabetic individuals are on the horizon.
In particular, the Targeting Aging with Metformin (TAME) trial, a large
placebo-controlled trial that has been designed to enroll 3000 subjects,
was launched in 2017. This study intends to compare the metformin users
with placebo controls, and might offer stronger evidence for the
protective role of metformin in cancer, cardiovascular disease and other
age-related diseases 98, 99.