S2411 Safety and Efficacy of Semaglutide in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Steatohepatitis (MASH): A Systematic Review and Meta-Analysis

Introduction: Semaglutide, a GLP-1 receptor agonist, has demonstrated potential in improving liver and metabolic outcomes. However, there is inconclusive data regarding its role in reducing hepatic steatosis and fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). This systematic review and meta-analysis aimed to assess the safety and efficacy of semaglutide in patients with MASLD and its progressive form, MASH. Methods: We conducted a comprehensive search of PubMed, Embase, Cochrane, Scopus, ClinicalTrials.gov, and ScienceDirect to retrieve interventional trials evaluating the use of semaglutide in MASLD or MASH. Outcomes included changes in controlled attenuation parameter (CAP) score, liver stiffness, liver enzymes (alanine aminotransferase [ALT]/aspartate aminotransferase [AST]), fibrosis scores (FIB-4), body mass index (BMI), hemoglobin A1c (HbA1c), and cholesterol levels. Both double- and single-arm meta-analyses were performed using a random-effects model in R, with sensitivity analyses and publication bias assessments. Results: Thirteen studies comprising 1,334 patients were included. In comparative analyses, semaglutide significantly reduced hepatic steatosis (CAP score: Mean Difference [MD] −20.88 dB/m; P = 0.0003), BMI (MD −2.17 kg/m²; P = 0.0004), HbA1c (MD −1.32%; P = 0.0004), ALT (MD −12.16 U/L; P < 0.0001), and AST (MD −10.00 U/L; P = 0.008). Liver stiffness reduction was non-significant initially (Standardized Mean Difference [SMD] −0.44; P = 0.078), but achieved significance upon the exclusion of an outlier, i.e., Newsome et al. 2020 (SMD −0.22; P = 0.022; I² = 0%). In single-arm analysis, semaglutide significantly improved CAP (MD −37.31 dB/m; P < 0.001), FIB-4 (MD −0.19; P = 0.03), BMI (MD −3.19 kg/m²; P < 0.001), HbA1c (MD −1.00%; P < 0.001), ALT (MD −19.32 U/L; P < 0.001), and AST (MD −12.80 U/L; P < 0.001). Cholesterol reduction was significant in single-arm studies (MD −14.55 mg/dL; P = 0.018) but not in comparative data (MD −3.00 mg/dL; P = 0.738). Heterogeneity ranged from moderate to high across most outcomes but was addressed through sensitivity analyses. Publication bias was minimal to moderate. Conclusion: Semaglutide significantly improves hepatic steatosis and metabolic parameters in patients with MASLD/MASH. However, its effect on fibrosis is limited and inconsistent, underscoring the need for longer trials that utilize histological endpoints. Semaglutide may be most beneficial in MASLD patients with diabetes mellitus or obesity as part of a broader therapeutic strategy.