Phenformin is an orally administered biguanide derivative with potential to lower blood glucose concentrations in patients with non-insulin-dependent diabetes mellitus. In general, biguanides improve insulin sensitivity and decrease insulin resistance by inhibiting complex 1 of the mitochondrial respiratory chain and inducing AMP-activated protein kinase (AMPK)-dependent signaling. Phenformin, however, has been withdrawn from clinical use because it also inhibits peripheral glucose oxidation and has an associated effect of inducing lactic acidosis when not metabolized sufficiently. Through AMPK activation, phenformin at 300 mg/kg exhibits anticancer activity by inhibiting the growth of MCF-7 and MDAMB231 breast cancer cell xenografts in mice.
