Abstract 15618: Incremental Cardiovascular Benefit of GLP-1 Therapy in Patients with HFrEF and Type 2 Diabetes on Quadruple GDMT
Abstract
Background: Patients with heart failure with reduced ejection fraction (HFrEF) and type 2 diabetes mellitus (T2DM) remain at high residual cardiovascular risk despite guideline-directed medical therapy (GDMT). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated cardiometabolic benefits, but their incremental role in patients already on quadruple GDMT remains poorly defined. We sought to evaluate cardiovascular outcomes associated with GLP-1RA use in this high-risk population. Methods: We conducted a retrospective cohort study using the TriNetX global federated research network. Adult patients (≥18 years) with ischemic cardiomyopathy, HFrEF (LVEF ≤40%), T2DM, and BMI ≥27 kg/m 2 on quadruple GDMT (beta-blocker, mineralocorticoid receptor antagonist, SGLT2 inhibitor, and ACEi/ARB/ARNI) were identified. Patients receiving GLP-1RA therapy were compared with those not receiving GLP-1RA. Propensity score matching (1:1) yielded 1,075 patients in each cohort. Outcomes were assessed over 1 year and included major adverse cardiovascular events (MACE), heart failure exacerbation, atrial fibrillation/flutter, ventricular arrhythmias, and myocardial infarction (MI). Results: At 1 year, GLP-1RA use was associated with significantly improved outcomes MACE 5.6% vs 15.7% (HR 3.15; p<0.001), Heart failure exacerbation: 14.2% vs 22.7% (HR 1.80; p=0.008), Atrial fibrillation/flutter 7.2% vs 11.1% (HR 1.65;p=0.015), Ventricular arrhythmias 6.5% vs 10.4% (HR 1.79; p=0.008), Myocardial infarction 4.6% vs 11.2% (HR 2.71; p=0.001), Kaplan-Meier analyses consistently demonstrated higher event-free survival in the GLP-1RA cohort across all endpoints. Conclusion: In patients with ischemic HFrEF and T2DM already receiving quadruple GDMT, the addition of GLP-1RA therapy is associated with significant reductions in major cardiovascular events at 1 year. These findings suggest a meaningful incremental benefit of GLP-1RA beyond contemporary GDMT, supporting further prospective evaluation of GLP-1RA as an adjunctive strategy in populations with advanced heart failure.