Metformin
Monograph · AMetformin (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.
How it clearsHalf cleared in ~6h. Most (~96%) gone by ~1d.
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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.
Interesting longevity signals with mechanistic plausibility — but most human data is still in early collection. The biology is real; the human response curve isn't fully mapped yet. Users in this tier are genuinely contributing to what becomes established evidence.
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.
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- AStrong evidence
Metformin is first-line pharmacotherapy for type 2 diabetes
1 supporting referencesVerified 23d 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.
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