Metformin: An AMPK-dependent antidiabetic drug with novel medical applications

Metformin (MET) is a well-known antidiabetic drug for type 2 diabetes mellitus (T2DM) treatment. The therapeutic effects of MET come from its ability to decrease both the production of hepatic glucose and its absorption via the intestine and improve insulin hormone sensitivity. This review aims to summarize the new medical applications of this old antidiabetic drug. Nowadays, MET is used in pre-clinical trials to treat cancer and slow the proliferation rate, emerging from its hypoglycemic effect and antioxidant activity. MET enhanced the functions of immune T-cells and reduced the proinflammatory mediators in macrophages. Moreover, based on the pre-clinical studies, its effect on the reproductive system is confirmed as MET showed an excellent candidate for polycystic ovary syndrome (PCOS) treatment and improved ovarian cyclicity, and reduces gestational diabetes risks in female; however, the effect on sperm number and motility is still in debate. Treatment with MET also showed some beneficial effects on bone health, and its administration led to a deficiency in vitamin B12. Furthermore, MET enhances anaerobic pathways and increases lactic acid levels. This review demonstrated the novel uses of MET in different clinical settings with explained mechanisms of action.