Metformin and metabolic diseases: a focus on hepatic aspects

Abstract

Metformin has been widely used as a first-line anti-diabetic medicine for the treatment of type 2 diabetes (T2D). As a drug that primarily targets the liver, metformin suppresses hepatic glucose production (HGP), serving as the main mechanism by which metformin improves hyperglycemia of T2D. Biochemically, metformin suppresses gluconeogenesis and stimulates glycolysis. Metformin also inhibits glycogenolysis, which is a pathway that critically contributes to elevated HGP. While generating beneficial effects on hyperglycemia, metformin also improves insulin resistance and corrects dyslipidemia in patients with T2D. These beneficial effects of metformin implicate a role for metformin in managing non-alcoholic fatty liver disease. As supported by the results from both human and animal studies, metformin improves hepatic steatosis and suppresses liver inflammation. Mechanistically, the beneficial effects of metformin on hepatic aspects are mediated through both adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways. In addition, metformin is generally safe and may also benefit patients with other chronic liver diseases.

Keywords

metformin / diabetes / hepatic steatosis / inflammatory response / insulin resistance

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Acknowledgements

This work was supported, in whole or in part, by National Natural Science Foundation of China (81100562/H0711) (to J.Z.), and National Key Basic Research Program of China (2012CB910402) (to Y. H.), ADA grant 1-13-BS-214-BR, AHA 12BGIA9050003, NIH/NIDDK grants (1R01DK095828; 1R01DK095862) (to C.W.).

Juan Zheng, Shih-Lung Woo, Xiang Hu, Rachel Botchlett, Lulu Chen, Yuqing Huo, and Chaodong Wu declare no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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