Metformin

Metformin is a prescription biguanide, not a supplement, and Avelor scores it only so people can see how the off-label longevity story compares to the actual evidence. Two very different evidence bases get conflated here and should not be. The APPROVED indication, glycemic control in type 2 diabetes, is strongly evidenced: UKPDS 34 randomized 753 overweight adults with newly diagnosed type 2 diabetes over a median 10.7 years and reported a 36% lower all-cause mortality risk in the metformin arm versus conventional diet policy (95% CI 9 to 55, p=0.011) (PMID: 9742977). The LONGEVITY hypothesis is a much thinner and largely observational case. A systematic review of 53 studies found metformin users had lower all-cause mortality than non-diabetic comparators (HR 0.93, 95% CI 0.88 to 0.99), but the authors flagged baseline differences that could bias the result (PMID: 28802803), and a collaborative meta-analysis restricted to 13 randomized controlled trials found no significant all-cause mortality effect (RR 0.94, 95% CI 0.79 to 1.12) and no cancer signal (RR 1.02, 95% CI 0.82 to 1.26) (PMID: 22875195). Much of the geroprotection literature is subject to immortal time and time-window bias, and the three observational studies that avoided those biases reported no effect on cancer incidence (PMID: 23173135). The lifespan-extension evidence is largely animal-only, and even there it is inconsistent: metformin extended lifespan in male mice at 0.1% of diet in one study (PMID: 23900241) but did not significantly extend lifespan in genetically heterogeneous mice in the NIA Interventions Testing Program at the same dietary concentration (PMID: 27312235). No completed randomized trial has shown that metformin extends human lifespan or healthspan in people without diabetes; the TAME trial was designed to test that question (PMID: 27304507). Known tradeoffs are real: metformin is associated with reduced vitamin B12 status in randomized data (PMID: 20488910) and blunted aerobic training adaptation in older adults (PMID: 30548390). Metformin requires a prescription and ongoing monitoring. Every decision about starting, dosing, or stopping it belongs to your prescriber, not to a scanner and not to this page.