Efficacy and safety of glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: A systematic review and meta-analysis

Abstract

New drugs are urgently needed for the treatment of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The aim of this meta-analysis was to evaluate the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in NAFLD/NASH. We searched the MEDLINE, Embase, and Cochrane Library Central to identify randomized controlled trials (RCTs) and observational studies that compared GLP-1RAs with a control treatment or baseline values with respect to efficacy and safety in patients with NAFLD/NASH. Mean differences (MDs) with 95% confidence intervals (CIs) and odds ratios (ORs) were pooled using a random-effect model. Six studies were eligible and included. Among the 329 NAFLD/NASH patients included in these studies, 277 patients had type 2 diabetes (T2D). GLP-1RA treatment produced significant reductions relative to baseline in liver histology scores for steatosis (MD, 0.80; 95% CI, 0.49 to 1.11), lobular inflammation (MD, 0.22; 95% CI, 0.00 to 0.45), hepatocellular ballooning (MD, 0.41; 95% CI, 0.15 to 0.67) and fibrosis (MD, 0.35; 95% CI, 0.00 to 0.70). Compared with placebo and positive agents, GLP-1RAs significantly reduced gamma-glutamyl transpeptidase (GGT) levels (MD, 13.8 U/L; 95% CI, 7.4 to 20.3; P<0.001). The reported major adverse events associated with GLP-1RA treatment included mild to moderate gastrointestinal discomfort that resolved within a few weeks. Our study suggests that in NASH patients, particularly patients with diabetes, GLP-1RAs may improve liver histology and reduce aminotransferase levels from baseline. Benefits of GLP-1RAs are considered to outweigh the risks in NAFLD/NASH patients with or without diabetes.