Metformin

Metformin's seven-decade safety profile in hundreds of millions of users makes it the most accessible geroprotective agent. Its AMPK activation via mitochondrial Complex I inhibition produces cascading longevity effects: mTOR suppression, reduced IGF-1 signaling, and enhanced autophagy. A 2026 analysis of 30,000 patients (PMC12223363) found type 2 diabetic women on metformin had 30% lower all-cause mortality before age 90 versus matched controls. The TAME trial, the first FDA-approved study with aging as a primary endpoint, is underway. Standard dosing is 500–1500 mg/day; extended release reduces gastrointestinal side effects affecting 30% of users.