钠-葡萄糖协同转运蛋白2抑制剂治疗2型糖尿病合并非酒精性脂肪性肝病有效性和安全性的Meta分析

Efficacy and safety of sodium-glucose co-transporter 2 inhibitors in treatment of type 2 diabetes mellitus with nonalcoholic fatty liver disease:A meta-analysis

目的系统评价钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂对2型糖尿病合并非酒精性脂肪性肝病的有效性和安全性。方法检索截至2020年3月外文数据库PubMed、Cohrane Library、Embase;中文数据库中国知网、维普、万方,检索关键词筛选符合条件的研究,根据量表评价文献质量,应用RevMan 5.3和Stata 15.0软件对数据进行Meta分析。结果共纳入9项队列研究和5项随机对照试验,共计605例患者。主要观察指标Meta分析结果显示:SGLT2抑制剂可显著降低队列研究中的ALT(MD=-24.22,95%CI:-29.54^-18.89,P<0.001)、HbA1c(MD=-0.53,95%CI:-0.74^-0.32,P<0.001);随机对照试验中的ALT(MD=-12.51,95%CI:-15.61^-9.41,P<0.001)和HbA1c(MD:-0.54,95%CI:-0.80^-0.27,P<0.001)水平,差异均具有统计学意义。次要观察指标:SGLT2抑制剂可明显改善患者BMI(P<0.001)、脂肪重量(P<0.001)、肝脏脂肪分数(P<0.001)、GGT(P<0.001)、空腹血糖(P<0.001)、血清铁蛋白(P<0.001)和血清Ⅳ型胶原蛋白7S(P=0.02)。另外AST的随机对照试验研究(P=0.16)和队列研究(P<0.001)Meta分析结果存在差异。服用SGLT2抑制剂后体液量减少事件[RR(95%CI):7.67(1.45~40.42),P=0.02]、尿路感染事件[RR(95%CI):4.27(1.11~16.43),P=0.03]、生殖系统感染事件[RR(95%CI):3.76(1.21~11.69),P=0.02]的发生率均有所上升。结论当前证据显示,SGLT2抑制剂可以降低2型糖尿病合并非酒精性脂肪性肝病患者体质量、血糖、肝酶、肝脏脂肪含量,同时对肝脏纤维化的改善有一定作用,但会增加患者体液量减少、泌尿生殖系统感染的风险,未来仍需更多研究进一步验证。

Objective To systematically review the efficacy and safety of sodium-glucose co-transporter 2(SGLT2)inhibitors in the treatment of type 2 diabetes mellitus(T2DM)with nonalcoholic fatty liver disease(NAFLD).Methods Foreign databases(PubMed,Cochrane Library,and Embase)and Chinese databases(CNKI,VIP,and Wanfang Data)were searched for articles published up to March 2020.Keywords were used to screen out eligible studies,related scales were used to evaluate the quality of articles,and RevMan 5.3 and Stata 15.0 were used to perform the meta-analysis.Results A total of 9 cohort studies and 5 randomized controlled trials(RCTs)were included,with 605 patients in total.The meta-analysis of main observation indices showed that SGLT2 inhibitors significantly inhibited alanine aminotransferase(ALT)(mean difference[MD]=-24.22,95%confidence interval[CI]:-29.54 to-18.89,P<0.001)and hemoglobin A1c(HbA1c)(MD=-0.53,95%CI:-0.74 to-0.32,P<0.001)in cohort studies,as well as ALT(MD=-12.51,95%CI:-15.61 to-9.41,P<0.001)and HbA1c(MD=-0.54,95%CI:-0.80 to-0.27,P<0.001)in RCTs.The analysis of secondary observation indices showed that SGLT2 inhibitors significantly improved body mass index(P<0.001),fat mass(P<0.001),hepatic fat fraction(P<0.001),gamma-glutamyl transpeptidase(P<0.001),fasting blood glucose(P<0.001),serum ferritin(P<0.001),and serum typeⅣcollagen 7S(P=0.02).There was a significant difference in the result of the meta-analysis of aspartate aminotransferase between RCTs(P=0.16)and cohort studies(P<0.001).After the administration of SGLT2 inhibitors,there were significant increases in the incidence rates of decreased body fluid volume(risk ratio[RR]=7.67,95%CI:1.45-40.42,P=0.02),urinary tract infection(RR=4.27,95%CI:1.11-16.43,P=0.03),and reproductive system infection(RR=3.76,95%CI:1.21-11.69,P=0.02).Conclusion Current evidence suggests that SGLT2 inhibitors can reduce body mass,blood glucose,liver enzymes,and liver fat content in patients with T2DM and NAFLD and improve liver fibrosis to a certain degree,but they can increase the risk of fluid loss and reproductive system infection in patients.More studies are needed for further verification.