Metformin: new insights on the mechanisms of action

Metformin is currently the drug of first choice for the treatment of T2D but its exact mechanism of action has not been fully elucidated. Met formin exerts its hypoglycemic effect by reducing hepatic glucose production through inhibition of gluconeogenesis, which is upregulated in type 2 diabetes. Inhibition of hepatic glucose production by metformin is mediated by inhibition of mitochondrial respiratory chain resulting in a decrease in cellular energy status. Activation of the energy sensor AMPK is dispensable for the inhibitory effect of metformin on hepatic gluconeogenesis. Beyond its hypoglycemic action, metformin was reported to lower macrovascular complications associated with type 2 diabetes by inducing cardio protection through activation of AMPK.