Adjunctive metformin for obesity and frailty in older people—puncturing inflated expectations?

Metformin, a biguanide that has been used to treat diabetes for over seven decades, has attracted considerable recent attention from researchers in the field of ageing. Metformin’s mechanism of action has long been unclear, but a 2023 review identified effects on multiple pathways relevant to ageing, including effects on mammalian target of mTOR(definition)-inhibiting drug studied for extending healthspan and lifespan." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">rapamycin(definition) (mTOR) signalling, mitochondrial function, senescent cell activity, and gut microbiome modulation.1 Human observational studies have associated metformin with a reduced incidence of age-related diseases across several organ systems and, in some animal models, with modest extensions in lifespan and healthspan(definition).