Glucagon-Like Peptide-1 Receptor Agonists and Anthracycline Therapy in Breast Cancer: A Real-World Propensity-Matched Analysis

Background: Anthracycline cardiotoxicity increases breast cancer morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve cardio-renal outcomes in diabetes, but their effect during anthracycline therapy is unknown. Objectives: To determine whether adding GLP-1RAs to anthracycline-based therapy reduces mortality and major cardio-renal events compared to anthracycline alone. Methods: We conducted a retrospective propensity-score–matched cohort study within the TriNetX Global Collaborative Network (146 health-care organizations) of adult females with breast cancer who received anthracyclines between 2005-2024. Cohort A received ≥1 GLP-1a (n = 1691); Cohort B did not (n = 1691). Outcomes were captured 1-1095 days after index and analyzed with Kaplan–Meier survival and Cox proportional-hazards models. Significance was defined as log-rank P < 0.05 with 95 % confidence intervals (CIs) excluding 1. Cohorts were also matched for medication use [ACE inhibitors, Angiotensin receptor blockers, Sodium glucose transporter -2 reuptake inhibitors, Furosemide, and Spironolactone use]. Results: Mean follow-up: 625 ± 379 vs 728 ± 398 days. GLP-1RA therapy lowered risk of all-cause death (HR 0.19, 0.148-0.247, P < 0.01), cardiac arrest (0.335, 0.12-0.92, P=0.03), atrial fibrillation (0.40, 0.22-0.73, P < 0.01), hospitalization (0.478, 0.39-0.59, P < 0.001), emergency-department visit (0.67, 0.54-0.84, P < 0.001), and progression to stage 4 or 5 chronic kidney disease (eGFR <30 mL/min 1.73 m2; 0.41, 0.29-0.56, P < 0.001) (Table 1). Conclusions: The findings suggest that GLP-1a medications may offer protective benefits beyond glucose control, potentially improving cardiovascular, renal, and overall survival outcomes in breast cancer patients undergoing anthracycline chemotherapy. These real-world data support prospective trials of GLP-1a agents as cardio-renal protective adjuncts in oncology domains. Next steps include conducting prospective clinical trials, exploring mechanisms of action, stratifying patient populations, and expanding research into other cancer types or therapies.