Overview
- The review published in August 2026 synthesizes cellular, animal and human studies and concludes metformin has multiple plausible anti‑aging mechanisms such as AMPK activation, inhibition of mitochondrial complex I, mTOR suppression, increased autophagy, and epigenetic effects.
- Animal experiments cited in the review report lifespan or tissue‑age marker benefits in worms, several mouse models, and male cynomolgus monkeys, providing the strongest preclinical support for geroprotective effects.
- Human evidence remains mixed because most observational studies sample people with diabetes and different trials use varied endpoints; the MeMeMe randomized trial lowered progression to type 2 diabetes but did not cut cancer, heart disease, or death.
- Key practical questions remain unanswered, including which dose and starting age might help people without diabetes, how long treatment would be needed, and how to monitor long‑term risks such as vitamin B12 deficiency and rare lactic acidosis.
- The review highlights the gut microbiome and epigenetic clocks as potential mediators and calls for adequately powered randomized trials with composite aging endpoints to test whether molecular shifts translate into real gains in healthy lifespan.