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Metformin and metabolic diseases: a focus on hepatic aspects

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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.

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Authors and Affiliations

  1. Department of Nutrition and Food Science, Texas A&M University, College Station, TX, 77843, USA

    Juan Zheng, Shih-Lung Woo, Xiang Hu, Rachel Botchlett & Chaodong Wu

  2. Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Juan Zheng, Xiang Hu & Lulu Chen

  3. Drug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, China

    Yuqing Huo

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Zheng, J., Woo, SL., Hu, X. et al. Metformin and metabolic diseases: a focus on hepatic aspects. Front. Med. 9, 173–186 (2015). https://doi.org/10.1007/s11684-015-0384-0

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