非酒精性脂肪肝合并2型糖尿病的降糖药物选择

Selection of antidiabetic drugs for nonalcoholic fatty liver with type 2 diabetes mellitus

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是常见的慢性肝病病因,在一般人群中的患病率约为20%~30%,但在2型糖尿病(type 2 diabetes mellitus,T2DM)患者中则达到55%。降糖药物可能在延缓疾病进展中起关键作用。二甲双胍在T2DM的治疗中是最常用的药物,对肝纤维化未见明显改善,但可用于NAFLD危险因素的治疗,如体重、转氨酶、胆固醇、糖化血红蛋白水平,且降低患者罹患肝癌的风险。噻唑烷二酮类药物在肝脏气球样变、小叶炎症和纤维化方面均有改善。胰高血糖素样肽-1受体激动剂中最常用的药物是利拉鲁肽,能显著降低转氨酶水平、改善肝细胞气球样变和脂肪变性。关于二肽基肽酶-4和钠-葡萄糖共转运蛋白-2抑制剂作用的资料较少。胰岛素的使用与实体肿瘤,尤其是肝细胞癌的发生可能相关。所有的降糖药物都可以安全地应用于代偿期肝硬化患者,而胰岛素则是肝硬化失代偿期的首选药物。本文就降糖药物治疗NAFLD的有效性和安全性进行综述。

Non-alcoholic fatty liver disease(NAFLD)is the most common cause of chronic liver disease,accounting for 20%~30%of general population and reaching a prevalence of 55%in patients with type 2 diabetes mellitus(T2 DM).Antidiabetic drugs could have a role in the progression reduction of the disease.Metformin is the most frequently used drug in the treatment of T2 DM.It has no significant improvement in liver fibrosis,but it can be used for the treatment of co-factors of NAFLD such as body weight,transaminase,cholesterol and HbA1 c levels.A possible protective role in hepatocellular carcinoma has been reported for metformin.Thiazolidinediones show an improvement in ballooning,lobular inflammation and fibrosis in the liver.The most commonly used drug of glucagonlike peptide-1 receptor agonists is liraglutide,which significantly improves transaminase levels,hepatocyte ballooning and steatosis.Little information is available on the effects of dipeptidyl peptidase-4(DPP-4)and sodiumglucose cotransporter(SGLT)-2 inhibitors.The use of insulin may be associated with the development of solid tumors,especially hepatocellular carcinoma(HCC).All antidiabetic drugs can be safely used in patients with compensated cirrhosis,while insulin is the preferred drug in decompensated Child-Pugh C cirrhosis.The aim of this review is to summarize evidence on efficacy and safety of antidiabetic drugs in patients with NAFLD.