Metformin: From Mechanisms of Action to Therapies

Marc Foretz (1) , Bruno Guigas (2) , Luc Bertrand (3) , Michael Pollak (4) , Benoit Viollet (1)

1 UMR_S567 / UMR 8104 - Institut Cochin
2 Department of Molecular Cell Biology
3 Pole of Cardiovascular Pathology and Cliniques Universitaires Saint-Luc
4 Cancer Prevention Research Unit, Department of Oncology

Metformin is currently the first-line drug treatment for type 2 diabetes. Besides its glucose-lowering effect, there is interest in actions of the drug of potential relevance to cardiovascular diseases and cancer. However, the underlying mechanisms of action remain elusive. Convincing data place energy metabolism at the center of metformin’s mechanism of action in diabetes and may also be of importance in cardiovascular diseases and cancer. Metformin-induced activation of the energy-sensor AMPK is well documented, but may not account for all actions of the drug. Here, we summarize current knowledge about the different AMPK-dependent and AMPK-independent mechanisms underlying metformin action.

Keywords: metformin; type 2 diabetes; cardiovascular diseases; cancer; treatment; biguanide; AMPK; Gluconeogenesis; Energy Metabolism; mitochondrial respiration; Review paper

Domains: Endocrinology and metabolism

Marc Foretz, Bruno Guigas, Luc Bertrand, Michael Pollak, Benoit Viollet. Metformin: From Mechanisms of Action to Therapies. Cell Metabolism, 2014, 20 (6), pp.953 - 966. ⟨10.1016/j.cmet.2014.09.018⟩. ⟨hal-01092553v2⟩