The efficacy of glucagon-like peptide 1 receptor agonists in patients with non-alcoholic fatty liver disease: a systematic review and meta-analysis of randomized controlled trials

Background: non-alcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of metabolic syndrome and is highly prevalent all over the world. New drugs are urgently needed for the treatment of NAFLD. The aim of this meta-analysis was to assess the efficacy of glucagon-like peptide 1 receptor agonists (GLP-1RAs) in patients with NAFLD. Method: English language publications in the PubMed, Cochrane Library, Embase and Web of Science databases were searched from inception to October 2019. All randomized controlled trials (RCTs) of GLP-1RAs treatment for NAFLD were considered. Standardized mean difference (SMD) with 95 % confidence intervals (CIs) were pooled using the fixed-effects or random-effects model. Results: six RCTs, involving 406 patients, were included in the analysis. A significant improvement was found in liver fat fraction (LFF) (SMD = -0.33, 95 % CI, -0.64 to -0.03, p = 0.034), body mass index (BMI) (SMD: -0.89, 95 % CI: -1.60 to -0.19, p = 0.012) and adiponectin (SMD: 0.66, 95 % CI: 0.37 to 0.95, p = 0.000) with GLP-1RAs treatment. There were no significant differences in serum alanine aminotransferase (ALT) (SMD: -0.52, 95 % CI: -1.04 to 0.01, p = 0.054) and aspartate transaminase (AST) (SMD: -0.20, 95 % CI: -0.54 to 0.15, p = 0.134) reduction between the GLP-1RAs and control groups. In the subgroup analysis, exenatide was associated with an improvement in serum ALT (SMD = -1.25, 95 % CI: -1.68 to -0.82, p = 0.000) and AST (SMD = -0.62, 95 % CI: -1.16 to -0.08, p = 0.024). Liraglutide was associated with a reduction in BMI (SMD = -0.44, 95 % CI: -0.77 to -0.11, p = 0.010) and an increase in adiponectin (SMD = -0.33, 95 % CI, -0.64 to -0.03, p = 0.034). Conclusion: our study suggested that GLP-1RAs may improve LFF, BMI and adiponectin in patients with NAFLD. Furthermore, the potential efficacy to treat NAFLD was also shown. More high-quality RCTs are needed to validate our findings. Keywords: Glucagon-like peptide 1 receptor agonists. Non-alcoholic fatty liver disease. Systematic review. Meta-analysis.