Zheng Juan, Woo Shih-Lung, Hu Xiang, Botchlett Rachel, Chen Lulu, Huo Yuqing, Wu Chaodong
Department of Nutrition and Food Science, Texas A&M University, College Station, TX, 77843, USA,
Front Med. 2015 Jun;9(2):173-86. doi: 10.1007/s11684-015-0384-0. Epub 2015 Feb 12.
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.
二甲双胍已被广泛用作治疗2型糖尿病（T2D）的一线抗糖尿病药物。作为一种主要作用于肝脏的药物，二甲双胍可抑制肝糖生成（HGP），这是其改善T2D患者高血糖的主要机制。从生化角度来看，二甲双胍可抑制糖异生并刺激糖酵解。二甲双胍还抑制糖原分解，这是导致HGP升高的关键途径。在对高血糖产生有益作用的同时，二甲双胍还可改善T2D患者的胰岛素抵抗并纠正血脂异常。二甲双胍的这些有益作用表明其在非酒精性脂肪性肝病的管理中发挥作用。人体和动物研究结果均支持这一点，二甲双胍可改善肝脂肪变性并抑制肝脏炎症。从机制上讲，二甲双胍对肝脏方面的有益作用是通过腺苷单磷酸激活的蛋白激酶（AMPK）依赖性和AMPK非依赖性途径介导的。此外，二甲双胍总体上是安全的，对其他慢性肝病患者也可能有益。
