Rankings / Longevity — Pharma (Off-Label)
Metformin
Longevity · Biguanide
Tier B
What this is
UKPDS showed 36% reduction in all-cause mortality in T2D. TAME trial ($75M, 3000 non-diabetic older adults) repeatedly delayed — FDA approved design but unfunded. 2019 Konopka data: may blunt exercise-induced mitochondrial adaptations.
Mechanism
Complex I mild inhibition → AMPK activation → mTOR inhibition; improved insulin sensitivity; possible gut microbiome effects; reduced hepatic gluconeogenesis
Dose & route
500-2000 mg/day PO; titrate from 500 mg with meals
Citations
- https://www.afar.org/tame-trial
- https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00085-5/fulltext
- https://pmc.ncbi.nlm.nih.gov/articles/PMC6779524/
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This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.