Metformin

Mechanism of Action

Metformin is a biguanide antidiabetic that reduces hepatic gluconeogenesis through mild inhibition of mitochondrial complex I, leading to AMPK activation. AMPK (5'-AMP-activated protein kinase) is a cellular energy sensor that, when activated, shifts cellular metabolism from anabolic to catabolic pathways: inhibiting mTOR, increasing fatty acid oxidation, enhancing insulin sensitivity, and promoting glucose uptake in skeletal muscle. Metformin also alters the gut microbiome and activates AMPK-independent pathways (e.g., mTORC1 inhibition via Rag GTPase). In research contexts, it is studied for longevity, cancer prevention, and metabolic syndrome.

Evidence Level

Clinical Trial - Human

6 studies published