Metformin, beyond an insulin sensitizer, targeting heart and pancreatic β cells

Metformin, a biguanide derivate, is known as the first-line antidiabetic agent for type 2 diabetes mellitus (T2DM) treatment. It reduces insulin resistance and decreases blood glucose concentration by inhibiting gluconeogenesis and suppressing hepatic glucose production with improved peripheral tissue insulin sensitivity. As an insulin sensitizer, metformin takes pleiotropic actions and exerts protective effects on multiple organs mainly in insulin-targeted tissues such as liver, muscle, and adipose tissues. Recent studies discover that metformin also plays essential roles in heart and pancreatic β cells - two important organs in metabolic regulation. Metformin not only protects T2DM patients from cardiovascular diseases and heart failure, but also restores insulin secretion activities and protects pancreatic β cells from lipotoxicity or glucotoxicity. Although accumulated evidence shed light on the metformin action, the precise mechanism of metformin is still under investigation. Further laboratory investigations and clinical trials are needed to pinpoint a map of metformin action. Based on recent findings, this review characterizes the beneficial role of metformin in cardiovascular diseases and pancreatic β cells.