| Background:Nonalcoholic fatty liver disease(NAFLD)is currently the most common liver disease,affecting roughly 25%of the general population,and reaches about 70%in patients affected by type 2 diabetes mellitus(T2DM)and obesity.Cohort studies demonstrated that NAFLD is an independent predictor of development of T2DM.This relationship is bidirectional,as T2DM substantially predicts the development of NAFLD.Glucagon-like peptide 1(GLP-1)receptor agonists,considered as a second-line treatment for T2DM,have further positive consequences such as cardio-protective effects.Thanks to its weight-lowering,glycemic-controlling effects,it produced improvement in liver fat content and showed potential in NAFLD.They also increase the risk of gastrointestinal symptoms,hypoglycemia and might result in acute pancreatitis.Therefore,the purpose of this meta-analysis is to evaluate the efficacy and safety of GLP-1 receptor agonists in NAFLD,including liver histology,liver function and some metabolic indexes like body mass index(BMI).Methods:We searched Pubmed,Embase,Chinese CBM and CNKI databases January2021 to collect clinical studies on the use of GLP-1 receptor agonists in patients with NAFLD,including randomized controlled trials,case series,prospective and retrospective studies.According to the standards drawn u Pin advance,the collection of relevant data and the quality evaluation were performed subsequently.The following indicators were evaluated:liver histology,including steatosis,intralobular inflammation,hepatic ballooning degeneration and fibrosis;alanine aminotransferase(ALT),aspartate aminotransferase(AST),γ-glutamyl transpeptidase(γ-GT).Secondary outcome indicators:BMI,glycated hemoglobin(Hb A1c),high sensitivity C-reactive protein(hs-CRP),insulin resistance index(HOMA-IR)and the adverse events.This study was performed in strict accordance with the guidelines of the Cochrane Reviewer’s Handbook and the PRISMA statement.The pooling of data was carried out by using Review Manager5.1.0 software.Result:A total of 10 studies,including 1287 patients,were included in this meta-analysis.Two studies used metformin only as control,two studies used lifestyle interventions,and the rest used other hypoglycemic drugs or placebos.Compared with the control group,GLP-1 receptor agonists could significantly improve liver histology and reduce ALT[WMD=-14.35,95%CI:(-19.30,-9.40),P<0.00001;I~2=70%)andγ-GT level[WMD=-13.65,95%CI:(-16.80,-10.50),P<0.00001;I~2=48%).BMI and hs-CRPwere significantly different from those in the control grou P(P<0.0001,P<0.00001)after GLP-1 receptor agonists treatment,but there were no significant effects on Hb A1c and HOMA-IR.Almost all studies recorded adverse events,and except for predictable gastrointestinal symptoms(nausea,vomiting,diarrhea and loss of appetite),GLP-1 receptor agonists was rarely interrupted by other adverse reactions.Conclusion:In NAFLD patients,GLP-1 receptor agonists treatment produced significant reductions relative to baseline in liver histology scores and may reduce ALT andγ-GT level from baseline,which associated with disease severity and histological change.Although a large number of randomized controlled trials with more outcomes are still needed,the available data provide a strong evidence that the use of GLP-1 receptor agonists in NAFLD patients has better histological and metabolic benefits,not only improving liver histology,but also improving liver functions,reduce weight and systemic inflammation,which show potential in NAFLD patients.There are few studies with placebo and histological data in related studies at present,and data on diet and exercise intervention is lacked.At the same time,the long-term risks of drug treatment are also unknown.Therefore,studies with larger sample sizes and more histology outcomes should be conducted,and it is necessary to determine whether GLP-1 receptor agonists can be used as a first-line therapy in NAFLD patients with or without T2DM. |
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