Metformin is widely used for the treatment of
type 2 diabetes mellitus. Although this
biguanide derivative has been used for more than 50 years, its mechanism of action has not been fully elucidated. In this article we describe the latest achievements concerning the mechanisms of
antihyperglycemic action of
metformin. They include: decrease of
glucose absorption in the small intestine, increase of
glucose transport into cells, decrease in the plasma
free fatty acid concentrations and inhibition of gluconeogenesis. Activation of
AMP-activated protein kinase (AMPK) plays an important role in these processes. The latest discoveries have revealed mechanisms of anti-atherosclerotic, hypotensive and anticancer action of
metformin and its impact on vein endothelial function. The pleiotropic actions of
metformin include impact on plasma
lipid profile, decrease of oxidative stress, and increase in plasma fibrinolytic activity. Although
metformin is not metabolized, the latest research has shown that it is actively transported into hepatocytes and renal tubular epithelium, by OCT1 (
organic cation transporter 1, encoded by the SLC22A1 gene) and OCT2 (
organic cation transporter 2, encoded by the SLC22A2 gene), respectively. However, MATE1 transporter (multidrug and toxin extrusion 1
protein) is encoded by the SLC47A1 gene and facilitates
metformin excretion from these cells into bile and urine.
Metformin transporter gene polymorphisms may contribute to significant variation in drug response. Further studies of mechanisms of
metformin action could contribute to its wider use for the prevention of
type 2 diabetes mellitus,
cancer, and Alzheimer’s disease, and for the treatment of
type 1 diabetes mellitus, and
polycystic ovary syndrome (PCOS).