After decades of successful use of metformin in diabetic patients, investigators have started evaluating its efficacy in other domains like ageing. Beyond improving glycemic control, metformin has pleiotropic actions that target many age-related mechanisms. Inflammatory markers, liketumor necrosis factor and interleukins, can activate many cellular processes that lead to cellular and tissue damage. Interleukin-6 can induce fibroblast proliferation and collagen production, causing cardiac remodelling. In addition, it can promote myocyte hypertrophy, depressed contractility and apoptosis.

It has been proposed that metformin alters inflammatory responses by suppressing NF-kB via AMP-activated protein kinase-dependent pathways. Besides, itdecreases the production of reactive oxygen species through reverse electron flux and through the mechanistic target of rapamycin, resulting in reduction in superoxide, which may otherwise cause DNA damage and mutations. Research involving experimental models indicate that metformin may increase lifespan, delay the process of ageing and offer protection for specific tissues. According to human observational studies, metformin seems to be an efficaciousagent for decreasing the risk of depression, cardiovascular diseases, frailty and cancer.Its potential has also been shown in reducing mild cognitive impairment.

The effect of this metforminon clinical ageing outcomes may be speculative. However, due to its favorable safety profile and long-term use, it could emerge as a promising therapeutic option against multimorbidity and ageing in people with or without diabetes.¹

Reference

1. Valencia WM, Palacio A, Tamariz L, et al. Metformin and ageing: improving ageing outcomes beyond glycaemic control. Diabetologia. 2017;60:1630–1638.