降糖药物在非酒精性脂肪性肝病中应用的进展

Progress of antidiabetic drugs in non-alcoholic fatty liver disease

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是一种多系统代谢性疾病,与胰岛素抵抗、2型糖尿病等密切相关,已成为严重危害健康的常见病、多发病。目前尚无明确的药物用于治疗NAFLD。降糖药物是最有潜力的药物之一,包括胰岛素增敏剂[噻唑烷二酮类药物(TZDs)、过氧化物酶体增殖物激活受体(PPAR)-α/γ和α/δ双重激动剂]、双胍类(二甲双胍)、人胰高血糖素样肽-1(GLP-1)类似物、钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂等。这些药物对控制体质量,减少肝脂肪含量、改善肝脂肪变性和气球样变,改善非酒精性脂肪性肝炎(NASH),减轻炎症反应,降低血糖、血脂,改善肝功能,提高抗氧化能力有一定的作用。TZDs(吡格列酮)是临床证据最充分、治疗机制最明确的药物,但因其安全性和耐受性而受限制。二甲双胍是一种安全的药物,但对NAFLD的作用存在争议。新型药物如PPAR-α/γ和α/δ双重激动剂(赛格列扎和GFT505)、利拉鲁肽(GLP-1类似物)等正处于临床试验中,数据显示其对NAFLD及NASH有良好的改善作用,且安全性好。需强调的是,改变不良生活方式和控制体重等措施仍是NAFLD的基本治疗措施。

Non-alcoholic fatty liver disease （NAFLD） is a multi-system metabolic disorder and is closely associated with insulin resistance and type 2 diabetes. It has become a common and frequently occurring disease that seriously affects health. Drugs have not been approved for the treatment of NAFLD. Antidiabetie drugs are one of the most promising drugs, including thiazolidinediones（ TDZs）, peroxisome proliferators-aetivated receptor（PPAR） agonists α/γand α/δ, biguanides （mefformin）, human glucagon-like peptide-1 （GLP-1） analogues, and sodium glueoseeo-transporter 2 （SGLT2） inhibitors, etc. These drugs have certain positive roles in controlling body weight, reducing liver fat content, improving hepatic steatosis and balloon degeneration, improving non alcoholic steatohepatitis （NASH）, reducing inflam- mation, lowering blood sugar, lowering blood lipids, improving liver function, and improving antioxidant capacity. TDZs （pioglitazone） have the most adequate clinical evidences and the most clear treatment mechanisms, but are limited by their safety and tolerability. Metformin is a safe drug, but the role of NAFLD is controversial. New drugs such as PPAR- α/γand α/δ double agonists （saroglitazar and GFT505 ）, liraglutide （GLP-1 analogue） are in clinical trials. The data show that they have good effects on NAFD and NASH, and the securities are good. NAFLD and NASH have favorable im- provement, and good safety. It should be emphasized that measures such as changing unhealthy lifestyles and weight con- trol are still the basic treatment measures for NAFLD.