Hepatoprotective activity of metformin: A new mission for an old drug?

Metformin, as a dimethyl biguanide prescribed as the first-line medication for treatment of type 2 diabetes mellitus, is one of the most frequently used drugs, worldwide. However, the beneficial effects of metformin are not limited to insulin sensitizing and blood glucose lowering effects as recent clinical trials deciphered lower cancer risk in metformin users. In addition, metformin protected the liver against chemical or viral hepatotoxicants through various mechanisms including activation of AMPK via inhibition of mitochondrial complex I, inhibition of mitogen activated protein kinase (MAPK) and inhibition of Smads phosphorylation. Clinical trials are under way to assess possible additive effects of metformin when co-administered along with the standard regimen for hepatocellular carcinoma (HCC) treatment. This review outlines the molecular mechanisms behind protective activity of metformin against different liver diseases.