Rankings / Longevity — Pharma (Off-Label)
Metformin
Longevity · Biguanide
Also known as: Glucophage ·Glumetza ·Fortamet ·Riomet
Tier B+
Bottom line
Read Off Label grades Metformin as B+ (7.2/10) based on strong evidence, variable benefit magnitude, and a low-med-risk safety profile.
UKPDS showed 36% reduction in all-cause mortality in T2D.
Typical use: 500-2000 mg/day PO; titrate from 500 mg with meals — Rx.
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/
- https://europepmc.org/article/PMC/12937842
- https://pubmed.ncbi.nlm.nih.gov/41736859/
- https://pubmed.ncbi.nlm.nih.gov/42010803/
- https://clinicaltrials.gov/study/NCT00941161
Links go to the source. If a link is dead or you want something re-checked, let me know.
Common questions
- Does Metformin work?
- Read Off Label rates the evidence for Metformin as Strong and the benefit magnitude as variable, producing an overall grade of B+ (7.2/10). UKPDS showed 36% reduction in all-cause mortality in T2D.
- Is Metformin safe?
- Metformin has a low-med risk profile in published human data. Legal status: Rx (off-label for longevity). This is not medical advice — see the disclaimer.
- What is the typical dose for Metformin?
- 500-2000 mg/day PO; titrate from 500 mg with meals
- How does Metformin work?
- Complex I mild inhibition → AMPK activation → mTOR inhibition; improved insulin sensitivity; possible gut microbiome effects; reduced hepatic gluconeogenesis
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.