Metformin
Metabolic / LongevityAlso known as: Glucophage, Metformin HCl, Metformin Hydrochloride, Fortamet, Glumetza, Riomet
Mechanism
Metformin is the world's most prescribed diabetes drug and is not a peptide, but it is frequently asked about in peptide communities due to its prominent role in longevity research. It improves insulin sensitivity, reduces hepatic glucose output, and activates AMPK — a master metabolic regulator. The landmark TAME (Targeting Aging with Metformin) trial is testing whether it can slow human aging. It synergizes well with many peptide protocols.
Technical detail
Metformin is a biguanide derivative (not a peptide) that activates AMP-activated protein kinase (AMPK) primarily through inhibition of mitochondrial complex I in hepatocytes, increasing the AMP:ATP ratio. AMPK activation suppresses hepatic gluconeogenesis (reducing fasting glucose by 20-30%), enhances peripheral glucose uptake, increases fatty acid oxidation, and inhibits mTORC1 signaling. Its longevity relevance stems from AMPK-mediated activation of autophagy, reduction of IGF-1 signaling, NF-κB-mediated inflammation suppression, and potential telomere preservation. Observational studies show reduced all-cause mortality in diabetics on metformin versus non-diabetic controls (Cardiff study). The TAME trial is the first FDA-approved aging-as-indication clinical trial.