Semaglutide versus other GLP-1 receptor agonists in patients with MASLD.

OBJECTIVES: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide. While glucagon-like peptide-1 receptor agonists (GLP-1RAs) show promise in MASLD treatment, the comparative effectiveness of semaglutide versus other GLP-1RAs remains unclear. This study aimed to compare clinical outcomes between semaglutide and other GLP-1RAs in patients with MASLD. METHODS: Using the TriNetX Research Network database, we conducted a retrospective cohort study of patients with MASLD newly prescribed GLP-1RAs between December 2017 and September 2023. The primary outcome was a composite of all-cause mortality, major adverse cardiovascular events, major adverse kidney events, and major adverse liver outcomes. Secondary outcomes included the individual components of the primary outcome. RESULTS: After propensity score matching, 20,384 patients were included in each group. Compared to other GLP-1RAs, semaglutide was associated with a 14% lower risk of primary composite outcomes (31.8 vs. 36.6 events per 10,000 person-years; adjusted HR, 0.86; 95% CI: 0.80-0.93). Semaglutide users showed significantly reduced risks of all-cause mortality (aHR, 0.68; 95% CI: 0.59-0.80) and major adverse liver outcomes (aHR, 0.79; 95% CI: 0.66-0.94). Benefits were consistent across subgroups, including age, sex, obesity status, and diabetes status. Comparative analyses showed superior outcomes with semaglutide versus dulaglutide (aHR, 0.88; 95% CI: 0.81-0.96) and liraglutide (aHR, 0.83; 95% CI: 0.71-0.97). CONCLUSIONS: In patients with MASLD, semaglutide use was associated with significantly better clinical outcomes compared to other GLP-1RAs, particularly in reducing mortality and major adverse liver outcome risks. These findings suggest semaglutide may be the preferred GLP-1RA choice for MASLD treatment.