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. 2025 Feb 10;15(1):4947.
doi: 10.1038/s41598-025-89408-z.

Glucagon-like peptide-1 receptor agonists improve metabolic dysfunction-associated steatotic liver disease outcomes

Brandon Havranek  1 , Rebecca Loh  2 , Beatriz Torre  3 , Rachel Redfield  2 , Dina Halegoua-DeMarzio  4
Affiliations

Glucagon-like peptide-1 receptor agonists improve metabolic dysfunction-associated steatotic liver disease outcomes

Brandon Havranek et al. Sci Rep. .

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease and is associated with significant cardiovascular morbidity and mortality. This study aims to investigate the association of glucagon-like peptide-1 (GLP-1) agonists with major cardiovascular events, clinically significant portal hypertension events, and all-cause mortality in patients with MASLD. A large, population-based retrospective cohort study was conducted using the TriNetX platform, which provided real-time access to electronic health records of 634,265 adult patients with MASLD/MASH. Propensity score matching (PSM) was employed to create two cohorts: A GLP-1 agonists group and a control group without GLP-1 agonists usage. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models along with Kaplan-Meier survival analyses to estimate outcomes at the end of 1, 3, 5, and 7 years. After PSM, 6,243 patients were included in each group. The GLP-1 agonist group had significantly lower risk of heart failure (at 7 years, HR, 0.721; 95% Cl, 0.593-0.876), composite cardiovascular events (at years 7, HR, 0.594; 95% Cl, 0.475-0.745), clinically significant portal hypertension events (at 7 years, HR, 0.463; 95% Cl, 0.348-0.611), and all-cause mortality (at 7 years, HR, 0.303; 95% Cl, 0.239-0.385). These results were consistent at 1-, 3-, 5-, and 7-years post index event. GLP-1 agonists usage in patients with MASLD is associated with reduced risk of major cardiovascular events, clinically significant portal hypertension, and all-cause mortality. These findings highlight the potential of GLP-1 agonists in MASLD/MASH management, warranting further prospective studies.

Keywords: Cardiovascular risk; Glucagon-like peptide-1 (GLP-1) receptor agonists; Liver disease; Metabolic dysfunction-associated steatotic liver disease (MASLD); Nonalcoholic fatty liver disease (NAFLD); Portal hypertension.

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Conflict of interest statement

Declarations. Conflict of interest: Dina Halegoua-DeMarzio: Consultant- Pfizer. Research Grant Support- Intercept, Galectin, BMS, Novo Nordisk, Viking, Pfizer; however, this article is solely the author’s work without any connection with Pfizer, Intercept, Galectin, BMS, Novo Nordisk, and Viking. All other authors have no conflict of interests. Ethical approval: Only aggregated counts and statistical summaries of de-identified information without any protected health information are received from participating HCOs, and no study-specific activities are performed in these retrospective analyses; therefore, TriNetX federated network has been granted a waiver from the Western institutional review board, including the Thomas Jefferson institutional review board.

Figures

Fig. 1
Fig. 1
Flowchart for selection of patients with diagnosis of MASLD/MASH with GLP-1 agonist usage and without.
Fig. 2
Fig. 2
Incidence of cardiovascular disease, clinically significant portal hypertension events, and all-cause mortality in the GLP-1 agonists group vs. the non-GLP-1 agonists control group at 1-, 3-, 5-, and 7-years post index event.
Fig. 3
Fig. 3
Association of patients with MAFLD and GLP-1 agonists with cardiovascular and clinically significant portal hypertension events. p values were calculated from Kaplan-Meier survival curves and were conducted using the log-rank test. The data shows statistically significant improvement in portal hypertension events, composite cardiovascular events, and new-onset heart failure in the group treated with GLP-1 agonists at all time points analyzed.
Fig. 4
Fig. 4
Association of GLP-1 agonists and all-cause mortality. p values were calculated from Kaplan-Meier survival curves and were conducted using the log-rank test. The data shows statistically significant improvement in all-cause mortality in the group treated with GLP-1 agonists at all time points analyzed.
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