GLP-1 receptor agonists for NAFLD treatment in patients with and without type 2 diabetes: an updated meta-analysis.

Background: Recent randomized controlled trials (RCTs) have tested the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RA) to specifically treat non-alcoholic fatty liver disease (NAFLD). Objective: We performed a meta-analysis of RCTs to investigate the efficacy of GLP-1 RAs for treatment of NAFLD or non-alcoholic steatohepatitis (NASH). Methods: We systematically searched PubMed and ClinicalTrials.Gov databases using pre-defined keywords to identify placebo-controlled or head-to-head RCTs (published until March 2020) of NAFLD individuals testing the efficacy of GLP-1 RAs to specifically treat NAFLD/NASH. Primary outcomes of interest included changes in serum liver enzymes, liver fat content, or histologic resolution of NASH. Weighted mean differences (WMD) were used to test the differences between the treatment arms. Results: We included 7 placebo-controlled or head-to-head RCTs involving a total of 472 middle-aged individuals (66% men; 77% with established diabetes) followed for a median of 16 weeks that used liraglutide or exenatide to treat NAFLD, as detected by imaging (n=6) or biopsy (n=1). Compared to placebo or reference therapy, treatment with GLP-1 RAs decreased serum alanine aminotransferase (n=7 studies; WMD: -8.77 IU/L, 95%CI -17.69 to 0.14 IU/L; I2=87.3%) and gamma-glutamyltransferase levels (n=4 studies; WMD: -10.17 IU/L, 95%CI -14.27 to -6.07 IU/L; I2=0%) and imaging-defined liver fat content (n=4 studies; WMD: -6.23%, 95%CI -8.95 to -3.51%; I2=85.9%). In one RCT involving 55 patients with biopsy-proven NASH, a 48-week treatment with liraglutide also led to a greater histological resolution of NASH than placebo. Conclusions: GLP-1 RAs (mostly liraglutide) seem to be a promising treatment option for NAFLD or NASH.