Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapieOct 31, 2026

GLP-1 receptor agonist treatment linked to heart health in patients with fatty liver disease

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Nov 2, 2026

Abstract

GLP-1 receptor agonist therapy was associated with a lower risk of adverse cardiovascular outcomes in patients with metabolic dysfunction-associated steatotic liver disease and type 2 diabetes.

42,910 patients were included in each treatment group after matching.
Compared to sulfonylurea therapy, GLP-1 RA therapy showed a hazard ratio of 0.87 for primary composite cardiovascular outcomes.
The association with cardiovascular outcomes was not statistically significant in 90-day and 180-day landmark analyses.
In a mouse model, GLP-1 RA treatment improved some measures of cardiac function and reduced signs of heart muscle cell enlargement.
Molecular analyses indicated lower expression of markers related to fibrosis and tissue remodeling, although myocardial fibrosis was not significantly different from control.
Further investigation is needed to clarify the effects of GLP-1 RA therapy on cardiac remodeling and cardiovascular risk.

Simplified

Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D) are at increased risk of adverse cardiovascular outcomes, potentially involving systemic metabolic dysfunction and cardiac remodeling. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve metabolic dysfunction in MASLD; however, their associations with cardiovascular outcomes and effects on MASLD-associated cardiac remodeling remain incompletely understood. In this translational study, we integrated a real-world TriNetX cohort of patients with MASLD and T2D with complementary experimental studies in a mouse model of MASLD. Following propensity score matching, 42,910 patients were included in each treatment group. GLP-1 RA therapy was associated with a lower risk of the primary composite cardiovascular outcome compared with sulfonylurea therapy (hazard ratio 0.87, 95% confidence interval 0.84-0.91; P < 0.001), although this association was not statistically significant in 90-day and 180-day landmark analyses. In Western diet-fed mice, GLP-1 RA treatment improved selected indices of cardiac function and attenuated cardiomyocyte hypertrophy. Although myocardial fibrosis was numerically reduced, the difference compared with vehicle-treated mice was not statistically significant (P = 0.28). Molecular analyses showed reduced expression of fibrosis- and extracellular matrix remodeling-related markers, including CTGF, TGF-β1, and vimentin. Collectively, GLP-1 RA therapy was associated with lower cardiovascular risk in the primary observational analysis, although this finding was not consistently supported by sensitivity analyses. Complementary experimental findings suggest improvements in selected cardiac functional indices and changes in fibrosis-associated molecular remodeling, warranting further investigation.

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GLP-1 receptor agonist treatment linked to heart health in patients with fatty liver disease

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