Semaglutide vs. other GLP-1RAs in MASLD: Real-world evidence

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Created On: 06/11/2025

Globally, the most commonly encountered chronic liver disease is metabolic dysfunction–associated steatotic liver disease (MASLD).

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Key take away

Semaglutide use in MASLD patients substantially reduces all-cause mortality and major liver complications when compared with other GLP-1RAs.

Background

Globally, the most commonly encountered chronic liver disease is metabolic dysfunction–associated steatotic liver disease (MASLD). Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) are emerging as promising therapies for MASLD, the relative effectiveness of semaglutide compared with other GLP-1RAs remains uncertain. Hence, this retrospective cohort analysis examined clinical outcomes linked with semaglutide versus other GLP-1RAs in MASLD.

Method

This study was carried out using data from the TriNetX Research Network, including individuals with MASLD who were newly prescribed GLP-1RAs. The key outcome was a composite measure including all-cause mortality, major adverse cardiovascular events (MACE), major adverse liver outcomes, and major adverse kidney events while secondary outcomes were defined as the individual components of this composite.

Result

Following propensity score matching, 20,384 participants were enrolled in each treatment group. Compared with other GLP-1RAs, semaglutide use was linked to a 14% lower risk of the composite primary outcome (31.8 vs. 36.6 events per 10,000 person-years; adjusted hazard ratio [HR] 0.86). Those receiving semaglutide also illustrated a markedly reduced risk of all-cause death (aHR 0.68) and major adverse liver outcomes (aHR 0.79). These advantages were consistent across subgroups as defined by age, gender, obesity, and diabetes status. In head-to-head comparisons, semaglutide was linked with better outcomes than liraglutide (aHR 0.83) and dulaglutide (aHR 0.88).

Conclusion

Among MASLD-affected patients, semaglutide was linked with improved clinical outcomes compared to other GLP-1RAs, particularly through reductions in overall mortality and adverse liver events. These findings support semaglutide as a potentially preferred GLP-1RA therapy in MASLD care.