The impact of glucagon-like peptide 1 agonists on anthracycline or human epidermal growth factor receptor 2 inhibitor-associated cardiotoxicity in patients with breast cancer and diabetes mellitus.

12026 Background: Anthracyclines or human epidermal growth factor receptor 2 (HER-2) inhibitors are associated with the potential for major adverse cardiovascular outcomes (MACE) among patients with breast cancer. Diabetes mellitus (DM) further increases the risk of MACE. Glucagon-like peptide 1 agonists (GLP1a) have been shown to improve MACE in the non-cancer population; however, there are no data testing whether GLP1a reduce the risk for MACE associated with anthracyclines or HER-2 inhibitors. Therefore, we hypothesized that GLP1a may decrease the risk for MACE among patients with breast cancer and DM receiving anthracycline or HER-2 inhibitors. Methods: We performed a retrospective, propensity score-matched cohort study using the TriNetX Analytics Network database, which contains de-identified data from over 120 participating healthcare institutions. We included adult breast cancer patients with type 2 DM who were treated with an anthracycline or HER-2 inhibitor therapy. We matched patients receiving a GLP1a with patients receiving non-GLP1a second-line diabetes medication based on the following variables: age, sex, pre-existing cardiac disease, the use of radiation, metastatic disease, cancer therapy, underlying comorbidities, and use of cardiovascular and diabetes medications. The primary outcome of interest, MACE, was defined as a composite of heart failure, myocardial infarction, and atrial fibrillation/flutter. Secondary outcomes included a composite of heart failure hospitalization and incident heart failure. Safety outcomes included all-cause mortality within 5 years of therapy initiation. Results: We matched 724 patients receiving a GLP1a treatment with patients receiving non-GLP1a treatment. The median age was 60 years for both cohorts. The prevalence of hypertension (81%), metastatic disease (61%), and radiation therapy (42%) was similar between cohorts, as was the use of anthracyclines and HER-2 inhibitors. In Cox proportional hazard analyses, the group receiving GLP1a treatment was associated with a lower risk of MACE (Hazard ratio (HR), 0.59 [95% CI: 0.41-0.86]), and heart failure hospitalization (HR, 0.56 [95% CI: 0.37-0.83]), and all-cause mortality (HR, 0.67 [95% CI: 0.48-0.93]) compared with non-GLP1a. Conclusions: GLP1a were associated with a reduction in major adverse cardiovascular events, incident heart failure and heart failure hospitalization, and all-cause mortality among anthracycline or HER-2 inhibitor-treated patients with breast cancer and DM. [Table: see text]