S2827 Comparative Efficacy of GLP-1 Receptor Agonists in the Treatment of Non-Alcoholic Steatohepatitis (NASH): A Systematic Review and Meta-Analysis

Introduction: Non-alcoholic steatohepatitis (NASH) is a progressive form of NAFLD associated with metabolic syndrome and carries a high risk of cirrhosis and cardiovascular morbidity. Recently, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as promising therapeutic agents due to their metabolic benefits, including weight loss and glycemic control. However, the relative effectiveness of individual GLP-1 RAs in improving liver histology in NASH remains under-investigated. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating GLP-1 RAs in adults with histologically confirmed NASH. Databases including PubMed, Embase, and Cochrane Central were searched through April 2025. Eligible studies compared GLP-1 RAs such as liraglutide, semaglutide, or dulaglutide against placebo and reported liver histologic endpoints. Primary outcomes were resolution of NASH without worsening of fibrosis and ≥1-stage fibrosis improvement. Pooled odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI) were calculated using a random-effects model. Results: Five RCTs encompassing 1,792 patients were included. Semaglutide showed the greatest likelihood of resolving NASH without fibrosis progression (OR 2.98; 95% CI: 1.92–4.72), while liraglutide also demonstrated significant benefit (OR 1.94; 95% CI: 1.39–2.89). Improvement in liver fibrosis by at least one stage was observed in 33% of patients on semaglutide versus 24% on liraglutide, compared to 19% in placebo groups. Weight reduction was most pronounced with semaglutide (MD –4.3 kg; 95% CI: –6.4 to –3.8), followed by liraglutide (MD –2.9 kg; 95% CI: –3.9 to –1.6). Gastrointestinal side effects such as nausea and bloating were common but generally self-limiting. Conclusion: GLP-1 receptor agonists, particularly semaglutide, demonstrate robust efficacy in histologic resolution of NASH and associated metabolic improvements. Liraglutide also provides meaningful benefits, although to a slightly lesser extent. These agents offer a dual advantage in targeting both liver disease and metabolic dysfunction. Despite tolerability concerns with GI symptoms, their favorable overall risk-benefit profile supports their potential role in future NASH treatment guidelines.