Real-World Cardiovascular Outcomes of GLP-1 Receptor Agonists in Women With Type 2 Diabetes and Breast Cancer.

Abstract

Introduction: The cardiovascular (CV) benefits of glucagon-like-peptide-1 receptor agonist (GLP-1 RA) therapies are not well-established in women with breast cancer and type 2 diabetes (T2D).

Objectives: The primary objective of this study was to compare the incidence of major adverse cardiovascular events (MACE) in women with T2D and breast cancer receiving GLP-1 RA therapy versus non-GLP-1 RA diabetes medications.

Methods: This retrospective study included women with T2D, diagnosed with breast cancer at ≥ 40 years old from December 16, 2014 to December 16, 2024 and having exposure to diabetes medications of interest (either GLP-1 RA or non-GLP-1 RA) within 5 years of these diagnoses. The primary end point, MACE, was a composite of myocardial infarction, ischemic stroke, coronary revascularization, cardiac arrest, or heart failure, within 5 years of the index date. Propensity score matching was performed. Participants were excluded from each individual outcome analysis if they had the outcome prior to the index date. Incidence rates, risk ratio (RR), 95% confidence interval (CI), and p-value were reported for each outcome.

Results: After matching, 19,608 patients were included in each cohort (mean age 64 years). Obesity and alkylating agents were more commonly reported in the GLP-1 RA cohort. Semaglutide was the most prescribed GLP-1 RA at index (45.1%). MACE occurred in 10.6% of the GLP-1 RA cohort and 13.4% of the non-GLP-1 cohort (RR 0.80, 95% CI 0.75-0.85, p < 0.001). Individual MACE end points, ischemic heart disease, and end-stage renal disease were significantly lower in the GLP-1 RA-treated cohort. GLP-1 RA use was also associated with a 61.6% relative risk reduction in all-cause mortality (RR 0.38, 95% CI 0.36-0.41, p < 0.001). Pancreatitis incidence was similar between groups (p = 0.057), whereas cholelithiasis was significantly lower with GLP-1 RA therapy (p < 0.001).

Conclusions: This study demonstrated the potential CV benefit of GLP-1 RA therapies among a population of female breast cancer survivors with T2D. Randomized trial data are needed to confirm these findings.