Definition

An extended-release (ER) tablet composed of the hydrochloride salt form of the biguanide metformin, with antihyperglycemic and potential prostate-cancer protective and antineoplastic activities. Upon oral administration, metformin targets and inhibits complex I (NADPH:ubiquinone oxidoreductase) of the mitochondrial respiratory chain and increases the cellular adenosine monophosphate (AMP) to adenosine triphosphate (ATP) ratio leading to activation of AMP-activated protein kinase (AMPK). This modulates AMPK-mediated transcription of target genes, which prevents hepatic gluconeogenesis, decreases intestinal absorption of glucose, enhances insulin sensitivity and fatty acid oxidation, and increases glucose uptake and utilization in target tissues. This lowers blood glucose levels. Metformin may exert antineoplastic effects through AMPK-mediated or AMPK-independent inhibition of mammalian target of rapamycin (mTOR), which is up-regulated in many cancer tissues. It also reduces cyclin D1. This inhibits cancer cell proliferation. Furthermore, this agent also inhibits tumor cell migration and invasion by inhibiting matrix metalloproteinase-9 (MMP-9) expression which is mediated through the suppression of transcription activator protein-1 (AP-1) activation. Also, metformin reduces hyperinsulinemia which may contribute to an anti-tumor effect. Metformin may increase the prostate-specific antigen (PSA) doubling time and may lower serum PSA levels.