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Comparative Study
. 2025 Jun 19;9(7):e0747.
doi: 10.1097/HC9.0000000000000747. eCollection 2025 Jul 1.

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

Chia-Chih Kuo  1 , Chun-Hsien Li  2 , Min-Hsiang Chuang  1 , Po-Yu Huang  1 , Hsing-Tao Kuo  1   3 , Chih-Cheng Lai  3   4
Affiliations
Comparative Study

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

Chia-Chih Kuo et al. Hepatol Commun. .

Abstract

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.

Keywords: glucagon-like peptide-1 receptor agonists; metabolic dysfunction–associated steatotic liver disease; real-world evidence; semaglutide.

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Conflict of interest statement

The authors have no conflicts to report.

Figures

FIGURE 1
FIGURE 1
Flowchart of patient selection in the study cohort for the semaglutide group and other GLP-1RA groups. Abbreviations: CKD, chronic kidney disease; ESKD, end-stage kidney disease; GLP-1RA, glucagon-like peptide-1 receptor agonists; MACE, major adverse cardiovascular events; MASLD, metabolic dysfunction–associated steatotic liver disease.
FIGURE 2
FIGURE 2
Kaplan-Meier curve for primary outcomes among the semaglutide and other GLP-1RA groups. Abbreviation: GLP-1RA, glucagon-like peptide-1 receptor agonists.
FIGURE 3
FIGURE 3
Subgroup analysis of primary outcomes between semaglutide and other GLP-1RAs. Abbreviations: GLP-1RA, glucagon-like peptide-1 receptor agonist; PY, person-year.
See this image and copyright information in PMC

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