P5852 - Comparative Efficacy of GLP-1 Receptor Agonists in the Treatment of Non-Alcoholic Steatohepatitis (NASH): A Systematic Review and Meta-Analysis

Aria Khan, MD¹, Shahzad Zafar, MD², Shahzaib Maqbool, MBBS³, Arslan Kareem, MBBS³, Umar Bazai, MD⁴
1NYC Health + Hospitals/Woodhull, Jamaica, NY; 2Howard University Hospital, Washington, DC; 3Rawalpindi Medical University, Rawalpindi, Punjab, Pakistan; 4Charleston Area Medical Centre, Charleston, WV

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.

Discussion: 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.

Disclosures:
Aria Khan indicated no relevant financial relationships.
Shahzad Zafar indicated no relevant financial relationships.
Shahzaib Maqbool indicated no relevant financial relationships.
Arslan Kareem indicated no relevant financial relationships.
Umar Bazai indicated no relevant financial relationships.

Aria Khan, MD¹, Shahzad Zafar, MD², Shahzaib Maqbool, MBBS³, Arslan Kareem, MBBS³, Umar Bazai, MD⁴. P5852 - Comparative Efficacy of GLP-1 Receptor Agonists in the Treatment of Non-Alcoholic Steatohepatitis (NASH): A Systematic Review and Meta-Analysis, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.