Meta-analysis finds metformin use associated with reduced mortality risk during up to 14 years of follow-up

Tuesday, September 12, 2017

A systematic review and meta-analysis in the November 2017 issue of Ageing Research Reviews documented a lower risk of cancer, cardiovascular disease, and all-cause mortality over follow-up among diabetics who were treated with the diabetes drug metformin in comparison with nonusers.

 “With the aging population of the developed world the extension of healthspan – the period that an individual is functional and free of chronic diseases – has been identified as an important goal both for the minimization of human suffering and to enable healthcare systems to cope,” write Jared M. Campbell of the University of Adelaide in Australia and his colleagues. “This systematic review aimed to identify and synthesize all research on the effect of metformin on all-cause mortality and diseases of aging which had the potential to give evidence on whether it could be used as a geroprotective factor to extend life and healthspan in the general population.”

The analysis included 53 studies, among which 13 reported data concerning mortality. It was determined that diabetics who used metformin had a 7% lower risk of all-cause mortality during up to 14 years of follow-up in comparison with nondiabetics and a 28% lower risk of all-cause mortality compared to diabetics who received non-metformin therapies. Metformin use was associated with a 32% lower risk of all-cause mortality compared to the use of insulin and a 20% lower risk in comparison with sulfonylurea drugs.

The risk of cardiovascular disease was 24% lower among metformin users in comparison with diabetics who received non-metformin therapies. Cancer risk in diabetics treated with metformin was 6% lower than that of nondiabetics.

The authors note that metformin has extended the lifespan of several organisms, possibly via decreases in insulin, IGF-1 signaling, reactive oxygen species levels, inflammation and DNA damage, as well as activation of AMP-activated protein kinase (AMPK). According to the authors, metformin’s effect on AMPK has received particular attention because it models intracellular mechanisms of caloric restriction. Two clinical trials examining the effects of metformin on aging are currently being planned.

“The apparent reductions in all-cause mortality and diseases of aging associated with metformin use suggest that metformin could be extending life and healthspans by acting as a geroprotective agent,” Dr Campbell and his associates conclude.


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