| Objective:To evaluate the efficacy and safety of glucagon-like peptide-1 receptor agonists(GLP-1 RAs)for treatment of nonalcoholic fatty liver disease(NAFLD).Methods:A computerized literature search in Pub Med,Cochrane Library,Web of Science,Embase database was performed up to December,2021,with English language restriction.We selected all randomized controlled trials(RCT)which met the inclusion and exclusion criteria,extracted the data and assessed the quality of trials.All statistical analyses were performed using Review Manager version 5.4.1.Results:12 RCTs reporting data on 1049 participants were finally eligible for this meta-analysis,of which used liraglutide(n=7 RCTs,204 participants),exenatide(n=3 RCTs,114 participants),dulaglutide(n=1 RCT,27 participants)or semaglutide(n=1 RCT,240 participants).The results of meta-analysis were as followed:(1)liver fat content(LFC)and the change of histology:compared with the control group,the GLP-1 RAs group showed a significant reduction in the liver fat content[weight mean difference(WMD)-4.24%,95%confidence interval(CI)-6.17,-2.31,P<0.0001],as well as with greater improvement in steatosis and hepatocyte ballooning[odds ratio(OR)4.08,95%CI 2.54,6.55,P<0.00001].However,no significant differences were observed in percentage of patients with liver fibrosis resolution(OR 1.47,95%CI 0.96,2.23,P=0.07).(2)Hepatic enzymes:compared with the control group,the GLP-1 RAs group showed significant reductions in alanine aminotransferase(ALT),aspartate transaminase(AST)andγ-glutamyl transferase(γ-GGT)(ALT:WMD-12.17 U/L,95%CI-16.68,-7.66,P<0.00001;AST:WMD-4.04 U/L,95%CI-6.69,-1.40,P=0.003;γ-GGT:WMD-13.73 U/L,95%CI-17.22,-10.24,P<0.00001).(3)Lipid profile:compared with the control group,the GLP-1 RAs group showed a significant reduction in triglycerides(TG)(WMD-0.19 mmol/L,95%CI-0.36,-0.03,P=0.02),but no significant differences were observed between the GLP-1 RAs group and the control group in the total cholesterol(TC),low-density lipoprotein(LDL)and high-density lipoprotein(HDL)(TC:WMD-0.09 mmol/L,95%CI-0.22,0.03,P=0.14;LDL:WMD-0.00 mmol/L,95%CI-0.15,0.15,P=0.97;HDL:WMD-0.00 mmol/L,95%CI-0.05,0.06,P=0.92).(4)Glucose metabolism indicators:compared with the control group,the GLP-1 RAs group showed significant reductions in fasting plasma glucose(FPG)and glycated hemoglobin A1c(HbA1c)(FPG:WMD-0.25 mmol/L,95%CI-0.41,-0.10,P=0.001;HbA1c:WMD-0.45%,95%CI-0.67,-0.22,P<0.0001);in contrast,no significan differences were observed between the GLP-1-RAs group and the control group in the homeostasis model assessment of insulin resistance(HOMA-IR)(WMD-0.19 mmol×U/L,95%CI-0.46,0.09,P=0.18).Nevertheless,subgroup analysis demonstrated that patients who underwent GLP-1RAs therapy for more than 24 weeks had significantly lower HOMA-IR levels(WMD-0.97 mmol×U/L,95%CI-1.50,-0.44,P=0.0004).(5)Body shape indicators:compared with the control group,the GLP-1 RAs group showed significant reductions in weight,body mass index(BMI),subcutaneous adipose tissue(SAT)and visceral adipose tissue(VAT)(Weight:WMD-3.58 Kg,95%CI-4.64,-2.53,P<0.00001;BMI:WMD-0.82 Kg/m~2,95%CI-1.08,-0.56,P<0.00001;SAT:WMD-35.29 cm~2,95%CI-47.15,-23.43,P<0.00001;VAT:WMD-39.37 cm~2,95%CI-47.62,-31.12,P<0.00001).(6)Adverse events:the GLP-1RAs group showed the incidence of gastrointestinal complications was higher than the control group(OR 3.07,95%CI 2.22,4.24,P<0.00001),but the incidence of hypoglycemia was lower than the control group(OR 0.35,95%CI 0.14,0.88,P=0.03).Conclusion:GLP-1 RAs is effective in reducing LFC,weight,BMI,SAT,VAT,serum hepatic enzymes,triglycerides,FBG and HbA1c.Besides,GLP-1 RAs led to histological resolution of nonalcoholic steatohepatitis.Although GLP-1 RAs significantly increased the risk of gastrointestinal adverse events,no serious treatment-related adverse events were reported.Treatment with GLP-1 RAs is a promising treatment option for NAFLD,warranting further studies. |
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