Evidence Level
Metformin's longevity potential is supported by strong observational data but lacks definitive interventional proof in non-diabetics. Bannister et al. (2014) published the landmark observational finding of 15% mortality reduction. The TAME trial (Targeting Aging with Metformin), led by Nir Barzilai, is the first FDA-approved trial specifically testing an anti-aging drug in humans — it will track composite age-related outcomes in ~3,000 participants aged 65-79. Gandini et al. (2014) meta-analyzed the cancer risk reduction data. The key controversy is Konopka et al. (2019), who showed metformin blunted exercise-induced mitochondrial improvements — raising questions about whether metformin's AMPK activation might compete with exercise's AMPK activation. This is a prescription medication and should only be used under medical supervision.