Metformin

What the evidence says

Metformin is approved to improve glycemic control in type 2 diabetes, not to slow aging. Proposed geroscience mechanisms involve energy sensing, mitochondrial signaling, AMPK- and mTOR-related pathways, and inflammation, but mechanistic plausibility is not a clinical outcome.^[8][3]

A 2017 review found lower mortality and age-related disease rates among metformin-treated people with diabetes. Those comparisons were dominated by observational data vulnerable to disease severity, treatment selection, and time-related bias; randomized cardiovascular estimates even in diabetes remained imprecise and crossed the null.^[1][2]

MILES found transcriptomic and metabolic changes after six weeks of metformin in only 14 older adults with impaired glucose tolerance. It demonstrated measurable biology, not slower aging, better function, disease prevention, or longer life.^[3]

Functional trials are cautionary. Metformin attenuated some mitochondrial adaptations to aerobic training; MET-PREVENT found no gait-speed benefit and poor tolerability in frail older adults; and the 2026 DEMFOS trial found no added physical-function benefit beyond intensive lifestyle treatment.^[4][6][7]

TAME helped define a trial strategy for testing whether metformin can delay a composite of age-related diseases, but a trial design is not an efficacy result. Label risks include gastrointestinal effects, vitamin B12 reduction, renal restrictions, and rare potentially fatal lactic acidosis.^[5][8]