Abstract PD8-05: A Retrospective Cohort Study on Mitigating Chemotherapy Side Effects in Breast Cancer Patients: The Role of GLP-1 Agonists

Abstract INTRODUCTION Chemotherapy-induced side effects account for over 25% of cancer-related morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), approved for diabetes management and weight loss, may also ameliorate treatment toxicity. This retrospective analysis evaluates whether concurrent GLP-1 RA use during chemotherapy in breast cancer(BC) patients improves tolerability, reduces complication rates, and enhances overall well-being, with the goal of informing novel supportive-care protocols. METHODS We queried the Global Collaborative Network using ICD-10 codes to identify BC patients treated with one or more of the following agents: doxorubicin, cyclophosphamide, paclitaxel, docetaxel, carboplatin, capecitabine, or gemcitabine. Patients receiving chemotherapy plus a GLP-1 RA were assigned to Cohort A (n = 5,685), and those on chemotherapy alone to Cohort B (n = 5,685). Propensity score matching adjusted for demographic and clinical confounders. The primary endpoint was the incidence of chemotherapy-related side effects and complications. Associations between GLP-1 RA use and adverse events were estimated via multivariate logistic regression. RESULTS Both cohorts comprised 5,685 patients; Cohort A had a mean age of 62 years (62.2% White, 18.6% Black, 9.5% Hispanic; 96% female; BMI 35.3 ± 7.5), and Cohort B a mean age of 63 years (62.7% White, 18.5% Black, 8.9% Hispanic; 96% female; BMI 29.3 ± 7.1). Adjusted analyses demonstrated that GLP-1 RA use was associated with significantly lower risks of anemia (RR 0.617, 95% CI 0.57-0.667; p 0.0001), neutropenia (RR 0.478, 95% CI 0.429-0.532; p 0.0001), thrombocytopenia (RR 0.587, 95% CI 0.514-0.671; p 0.0001), sepsis (RR 0.679, 95% CI 0.599-0.769; p 0.0001), nausea and vomiting (RR 0.711, 95% CI 0.656-0.772; p 0.0001), diarrhea (RR 0.763, 95% CI 0.699-0.834; p 0.0001), venous thromboembolism (RR 0.592, 95% CI 0.5-0.701; p 0.0001), mucositis (RR 0.440, 95% CI 0.374-0.519; p 0.0001), fatigue (RR 0.755, 95% CI 0.684-0.834; p 0.0001), hot flashes (RR 0.610, 95% CI 0.531-0.699; p 0.0001), myalgia/arthralgia (RR 0.837, 95% CI 0.745-0.939; p = 0.0024), cardiomyopathy (RR 0.651, 95% CI 0.543-0.780; p 0.0001), neuropathy (RR 0.717, 95% CI 0.664-0.776; p 0.0001), elevated liver enzymes (RR 0.608, 95% CI 0.516-0.716; p 0.0001), and fever (RR 0.629, 95% CI 0.565-0.701; p 0.0001). CONCLUSION In this large retrospective cohort, GLP-1 RA use was associated with significant reductions in hematologic, gastrointestinal, cardiovascular, and systemic toxicities among breast cancer patients receiving chemotherapy. These findings support the investigation of GLP-1 RAs as adjunctive agents in oncology supportive care. Prospective trials are needed to confirm these benefits and explore the underlying mechanisms, with the goal of integrating GLP-1 RAs into protocols to reduce treatment-related morbidity and improve patient outcomes. Citation Format: E. Obomanu, C. Jones, A. Ratnani, C. Ugwu, M. Megiso, T. Verinumbe, S. King, A. Ramkissoon, C. Dourado. A Retrospective Cohort Study on Mitigating Chemotherapy Side Effects in Breast Cancer Patients: The Role of GLP-1 Agonists abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD8-05.