Metformin (off-label longevity)
Biguanide. Inhibits hepatic glucose production via complex I of the mitochondrial electron transport chain. At longevity doses, also activates AMPK and reduces mTORC1 signaling.
TAME trial (Targeting Aging with Metformin) is the first longevity RCT in humans — in progress. Observational data in T2DM patients shows reduced all-cause mortality vs. non-diabetic controls (the Bradford Hill confound). Bryan Johnson and other longevity personalities take 500–2000 mg/day off-label. Robustly lowers IGFBP-1, modulates inflammation markers.
GI side effects common at initiation (take with food, titrate up). Reduces vitamin B12 absorption — supplement B12 on long-term use. Contraindicated in kidney disease (eGFR < 30). May blunt exercise adaptations (Musi 2020 finding — context-dependent). Lactic acidosis risk is overstated at standard doses.
Per-claim grading. Each claim is graded independently — same peptide, different claims can carry different grades.
- CLimited evidence
Metformin (off-label longevity) — primary mechanism: biguanide. inhibits hepatic glucose production via complex i of the mitochondrial electron transport chain. at longevity doses, also activates ampk and reduces mtorc1 signaling.
2 supporting referencesVerified 5d ago
External links to PubMed searches, ClinicalTrials.gov, and FDA materials. We do not host papers — we point at canonical sources.
FDA-approved for T2DM. Off-label for longevity — requires prescription.