Metformin has been shown in various studies to reduce all cause mortality, and it has been extensively studied for its impact of use and to the molecular mechanisms of its operations.
Metformin has been listing in 1989 clinical trials, but only mentioned in 3 clinical trials on longevity: 1) The Metformin In Longevity Study; 2) Metformin and Longevity Genes In Pre-Diabetics; and 3) Metformin And Longevity.
The Targeting Aging With Metformin is a clinical trial being sponsored by the American Federation of Aging Research which has been approved by the FDA. This will include 2 populations of subjects on of 1500 receiving metformin and another on placebo to investigate whether metformin delays onset of age related diseases ot precursor to conditions. Subjects will be in the age group of 70-80, residing within the USA who will be followed for 5 years.
The TAME trial was first discussed with the FDA in 2014, but is still waiting funding to investigate the longevity impacts of normal healthy people taking metformin.
Metformin used to be tops on all lists for reducing all cause mortality, but it has been knocked down a few notches with data on fish oils, PCSK9 inhibitors, testosterone, and SGLT2 inhibitors.
One 20 year old prospective study of metformin vs other conventional therapies for type 2 diabetes which included over 5,000 patients showed a 36% reduction in all cause mortality as compared to conventional therapy.
However not all studies show such a dramatic effect. Diabetics using metformin monotherapy vs sulfonylurea therapy studies have shown a 58% higher all cause mortality in those on sulfonylureas. Older men with prostate cancer and diabetes using metformin had a 24% ACMR in the first 6 months and reduction in prostate cancer specific mortality of 24%, however this effect waned over time.
Meta- analysis of papers on metformin and cancer show a 57% decrease in incidence of cancer and mortality in diabetic patients on metformin vs other conventional drugs; whereas insulin therapy dramatically increased the risk of cancer in diabetics by 69-363%.
Death by several cause may be reduced by metformin, studies continue to supply evidence backing this. However if there will be as significant beneficial effects in non-diabetics who are put on metformin for anti-aging reasons will still have to wait for the TAME trial to receive funding and the many years it will take to complete the study to answer those questions. In the meantime, metformin is cheap, cost effective, and has few side effects except for lactic acidosis.