Safety of glucagon-like peptide-1 receptor agonists in patients with breast cancer: A real-world multicenter cohort study.

11139 Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for patients with breast cancer and coexisting type 2 diabetes mellitus (T2DM). While GLP-1RAs have demonstrated metabolic and cardiovascular benefits in the general population, data regarding their safety in patients with breast cancer remain limited. Methods: We conducted a retrospective cohort study using the TriNetX Research Network, which aggregates de-identified electronic health record data from over 140 international healthcare organizations. Adult patients (≥18 years) with breast cancer who received breast cancer–directed systemic therapy and antidiabetic medications were included. The exposed cohort comprised patients who received a GLP-1RA within 90 days of systemic therapy initiation, while the comparator cohort included patients who received non–GLP-1RA antidiabetic agents. To minimize confounding, 1:1 propensity score matching was performed using demographics, body mass index, hemoglobin A1c, metastatic disease, breast cancer-directed therapy, and comorbidities. Outcomes were evaluated over 12 months using Cox proportional hazards models. Primary safety outcomes included adverse events commonly associated with GLP-1RA use: pancreatitis, biliary disease, and gastrointestinal adverse events (gastroesophageal reflux disease [GERD], bowel obstruction, and nausea/vomiting). Secondary outcomes included all-cause mortality and major adverse cardiovascular events (MACE), defined as a composite of myocardial infarction, ischemic stroke, and cardiovascular death. Results: A total of 29,380 patients with breast cancer and T2DM were identified. After propensity score matching, 3,796 patients were included in each cohort. Over 12 months of follow-up, GLP-1RA use was not associated with an increased risk of pancreatitis compared with non–GLP-1RA use (hazard ratio [HR], 1.20; 95% confidence interval [CI], 0.53–2.71). No significant differences were observed in biliary disease (HR, 0.93; 95% CI, 0.60–1.45) or bowel obstruction (HR, 0.70; 95% CI, 0.40–1.23). GLP-1RA use was associated with higher risks of GERD (HR, 1.48; 95% CI, 1.14–1.92) and nausea/vomiting (HR, 1.59; 95% CI, 1.26–2.00). Importantly, GLP-1RA use was associated with a lower risk of MACE (HR, 0.76; 95% CI, 0.59–0.99) and all-cause mortality (HR, 0.51; 95% CI, 0.37–0.69). Conclusions: In this study, GLP-1RA use was not associated with increased risks of serious gastrointestinal or biliary adverse events among patients with breast cancer receiving systemic therapy. While nausea/vomiting and GERD were more frequent, GLP-1RA use was associated with significant reductions in major adverse cardiovascular events and all-cause mortality. Prospective studies are warranted to confirm long-term safety and oncologic outcomes.