Metformin

Metformin is a biguanide oral antidiabetic drug, first-line therapy for type 2 diabetes mellitus. It lowers hepatic gluconeogenesis and improves insulin sensitivity, partly via mitochondrial complex I inhibition and indirect AMPK activation. Observational data suggest reduced all-cause mortality and cancer incidence in diabetics, motivating the proposed TAME trial (Targeting Aging with Metformin), which as of mid-2026 has not yet enrolled at scale, with funding and protocol revisions ongoing. Off-label longevity use remains investigational; benefit in metabolically healthy people is unproven and may even blunt exercise adaptations.