AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
GLP-1 Receptor Agonists and Cardiovascular Outcomes in MASLD: A Systematic Review and Meta-Analysis of Observational Studies
By Saha S, Jha A, Thakur A et al.
Introduction: Cardiovascular disease is a leading cause of morbidity and mortality in metabolic dysfunction-associated steatotic liver disease (MASLD). GLP-1 receptor agonists (GLP-1 RAs) reduce hepatic fibrosis in metabolic dysfunction-associated steatohepatitis (e.g., with semaglutide) and have established cardiovascular benefit in patients with type 2 diabetes. However, their cardiovascular effects in MASLD remain less well defined. We performed a systematic review and meta-analysis of observational studies evaluating the association between GLP-1 RA use and cardiovascular outcomes in adults with MASLD. Methods: PubMed and Embase were searched for observational studies of adults with MASLD, MASH, NAFLD, or NASH comparing GLP-1 RA therapy with any pharmacologic comparator, placebo, or usual care. Outcomes included MACE, heart failure hospitalization, and all-cause mortality. Pooled adjusted effect estimates were generated using random-effects models in RevMan 5.4.1, with I ² to assess heterogeneity. Subgroup analyses were performed by comparator type (placebo/no GLP-1 RA vs. other antidiabetics including SGLT2 inhibitors and DPP-4 inhibitors). Results: Seven observational studies were included in the MACE analysis. GLP-1 RA was associated with reduced MACE risk (HR 0.80, 95% CI 0.70-0.92; p=0.001; I ² =95%); non-significant versus placebo/no GLP-1 RA (HR 0.82, 95% CI 0.62-1.08) but significant versus other antidiabetics (HR 0.78, 95% CI 0.65-0.94). Heart failure hospitalization (5 studies) was reduced (HR 0.83, 95% CI 0.73-0.95; p=0.008; I ² =85%), significant versus placebo/no GLP-1 RA (HR 0.79, 95% CI 0.71-0.87) but not versus other antidiabetics (HR 0.88, 95% CI 0.74-1.05). All-cause mortality (6 studies) was lower with GLP-1 RA (HR 0.51, 95% CI 0.38-0.68; p<0.00001; I ² =97%), with reductions versus placebo/no GLP-1 RA (HR 0.37, 95% CI 0.25-0.55) and other antidiabetics (HR 0.62, 95% CI 0.45-0.86). Discussion: In adults with MASLD, GLP-1 RA-containing therapy was associated with lower risks of MACE, heart failure, and all-cause mortality. This suggests that MASLD represents a particularly high-risk cardiometabolic subgroup in whom GLP-1 RA therapy could provide meaningful cardiovascular benefit in addition to liver-related outcomes. Interpretation is limited by observational design, high heterogeneity, variable comparator definitions, and inclusion of combination-treatment comparisons. Prospective studies are needed to determine whether GLP-1 RAs improve cardiovascular outcomes specifically in MASLD populations.