Metformin
Activates AMPK via inhibition of mitochondrial complex I, reducing hepatic glucose output and improving peripheral insulin sensitivity. Secondary effects include suppression of mTORC1 signaling and upregulation of autophagy, which drive the longevity interest beyond its diabetic indication.
Three tiers ordered by aggressiveness. Tier chips on every OPTIMIZE intervention let you filter the catalog by your evidence tolerance.
- fasting-glucose
- hba1c
- fasting-insulin
- homa-ir
- vitamin-d
- creatinine
- egfr
- renal-impairment
- metabolic-acidosis
- alcohol-use-disorder
- hepatic-failure
- PMID:28802803Metformin as a Tool to Target Aging — Cell Metab, 2016
- PMID:31626474Targeting Ageing with Metformin (TAME) trial design — Am J Geriatr Pharmacother, 2019
- PMID:24577297Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls — Diabetes Obes Metab, 2014
Metformin is the oldest molecule with the youngest ambition. Approved in 1957 for diabetes. Now the subject of the TAME trial to become the first FDA-approved anti-aging drug. The pharmacology is straightforward. AMPK activation, mTOR suppression, glucose regulation. What makes it interesting is scale. Billions of patient-years of safety data. No other longevity candidate has that depth of evidence. The debate is not whether it works for diabetes. The debate is whether a 3-cent pill can extend healthspan in people who are not diabetic. That question is worth asking precisely because the downside risk is so well characterized.
This is not medical advice
Discuss with a licensed clinician before starting, stopping, or changing any compound. This page documents what the research literature describes — it is not a prescription.
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