BACKGROUND: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D) are at high cardiovascular risk. Whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) provide cardiovascular protection comparable to sodium-glucose cotransporter-2 inhibitors (SGLT2is) remain uncertain.
METHODS: Using the TriNetX global health research network, we conducted a retrospective cohort study of adults with MASLD and T2D initiating GLP-1 RAs or SGLT2is between 2017 and 2025. Propensity score matching balanced demographics, comorbidities, medications, and laboratory variables. Outcomes were analyzed using Cox proportional-hazards models, Kaplan-Meier curves, landmark analyses, negative control outcomes, and E-value estimation. Target-trial emulation principles were applied to reduce immortal-time and confounding bias.
RESULTS: After matching, 52,094 patients were included (mean age 58.5 years; 49.7% women) with a median follow-up of 3.0 years. GLP-1 RA use was associated with a lower risk of major adverse cardiovascular and cerebrovascular events compared with SGLT2is (HR 0.86, 95% CI 0.80-0.92; p < 0.001). Risks of heart failure, myocardial infarction, stroke, and all-cause mortality were also significantly reduced. Results were consistent across sensitivity analyses.
CONCLUSIONS: Among patients with MASLD and T2D, GLP-1 RA therapy was associated with a lower risk of cardiovascular events than SGLT2is, providing real-world comparative evidence in this population.
