Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis

This systematic review investigated whether the insulin sensitiser metformin has a geroprotective effect in humans. Pubmed and Embase were searched along with databases of unpublished studies. Eligible research investigated the effect of metformin on all-cause mortality or diseases of ageing relative to non-diabetic populations or diabetics receiving other therapies with adjustment for disease control achieved. Overall, 260 full-texts were reviewed and 53 met the inclusion criteria. Diabetics taking metformin had significantly lower all-cause mortality than non-diabetics (hazard ratio (HR) = 0.93, 95%CI 0.88-0.99), as did diabetics taking metformin compared to diabetics receiving non-metformin therapies (HR = 0.72, 95%CI 0.65-0.80), insulin (HR = 0.68, 95%CI 0.63-0.75) or sulphonylurea (HR = 0.80, 95%CI 0.66-0.97). Metformin users also had reduced cancer compared to non-diabetics (rate ratio = 0.94, 95%CI 0.92-0.97) and cardiovascular disease (CVD) compared to diabetics receiving non-metformin therapies (HR = 0.76, 95%CI 0.66-0.87) or insulin (HR = 0.78, 95%CI 0.73-0.83). Differences in baseline characteristics were observed which had the potential to bias findings, although statistical adjustments were made. The apparent reductions in all-cause mortality and diseases of ageing associated with metformin use suggest that metformin could be extending life and healthspans by acting as a geroprotective agent.