新型降糖药治疗非酒精性脂肪性肝病研究进展

Research Progress of New Hypoglycemic Drugs for Nonalcoholic Fatty Liver Disease

非酒精性脂肪性肝病(NAFLD)与2型糖尿病密切相关,两者互为危险因素,胰岛素抵抗可能是两者共同的发病机制。研究发现,PPAR激动剂、SGLT2抑制剂和GLP-1R激动剂等已上市新型降糖药除有效改善血糖外,对脂肪肝也有很好的疗效。Saroglitazar是一款PPARα/γ双重激动剂,2020年被印度药品管理总局批准用于治疗2型糖尿病和NAFLD。达格列净、Semaglutide在Ⅱ期临床研究中可显著改善NAFLD患者肝脏脂质沉积和炎症反应,目前正处于治疗NAFLD的Ⅲ期临床研究阶段,未来可能成为治疗2型糖尿病合并NAFLD的基础药物。现就新型降糖药治疗NAFLD作一综述,以期对后续NAFLD新药开发和临床合理用药提供参考。

Nonalcoholic fatty liver disease(NAFLD)is closely associated with type 2 diabetes.They are dangerous factors for each other,and insulin resistance may be a common pathogenesis for both.It has been found that some newly approved hypoglycemic drugs,such as peroxisome proliferator-activated receptor agonists,inhibitors of type 2 sodium-glucose co-transporter as well as glucagon-like peptide-1 receptor agonists,not only improve the blood glucose effectively,but also have great therapeutic effects on fatty liver.As a dual PPAR α/γ agonist,Saroglitazar was approved by Drug Controller General of India for type 2 diabetes and NAFLD in 2020.In the second phase clinical trials,dapagliflozin and semaglutide obviously improved the hepatic lipid deposition and inflammation for patients of NAFLD,they are both in the third phase clinical trials currently and may become the basic drugs for type 2 diabetes combined with NAFLD in the future.This paper reviews the use of new hypoglycemic drugs in nonalcoholic fatty liver disease,so as to provide references for subsequent development of new drugs and rational clinical medication.