Beyond cardio-renal outcomes with GLP-1RA and SGLT2i in anthracycline-treated diabetic women with breast cancer: A propensity score–matched analysis from Global Federated Health Research Network.

Abstract

e23079 Background: Anthracyclines remain central to breast cancer therapy but are associated with cardiotoxicity and downstream morbidity. In women with diabetes mellitus, GLP-1 receptor agonists (GLP-1RA) and sodium–glucose cotransporter-2 inhibitors (SGLT2i) may influence outcomes beyond cardio-renal endpoints. We evaluated clinically relevant events (cytopenias, infections, venous thromboembolism, polyneuropathy, mood disorders) in addition to cardio-renal outcomes in anthracycline-treated women with breast cancer and diabetes. Methods: Using the TriNetX Global Collaborative Network, we identified women ≥18 years with breast cancer, diabetes mellitus, and anthracycline exposure. Three 1:1 propensity-matched comparisons were performed: (1) SGLT2i without GLP-1RA vs neither exposure (n = 934/arm), (2) GLP-1RA without SGLT2i vs neither exposure (n = 982/arm), and (3) GLP-1RA vs SGLT2i (n = 703/arm). Matching included demographics, cardiometabolic comorbidities, antihyperglycemic medications, and cancer therapies along with radiation therapy. Outcomes were assessed through 3 years post-index using time-to-event analyses; HRs with 95% CIs are reported. Results: Versus neither exposure, SGLT2i was associated with lower hazard of severe cytopenias (Hb < 8 g/dL, neutropenia and platelets < 50,000/µL), sepsis (0.615, 0.478 - 0.792), neutropenic fever (0.419, 0.283 - 0.622), VTE (DVT: 0.673, 0.468 - 0.967; PE: 0.603, 0.414 - 0.878), polyneuropathy (0.822, 0.687 - 0.984) and mood disorders (0.743, 0.608 - 0.907). GLP-1RA exposure versus neither exposure was associated with lower cytopenias, sepsis (0.553, 0.423 - 0.724), neutropenic fever (0.419, 0.283 - 0.622), and VTE outcomes (DVT: 0.654, 0.468 - 0.914; PE: 0.449, 0.307 - 0.655). In head-to-head analyses, GLP-1RA demonstrated lower hazard of heart failure (0.505, 0.389 - 0.656), cardiomyopathy (0.396, 0.273 - 0.574), AKI (0.704, 0.531 - 0.934), hospital visits (0.862, 0.752 - 0.989), and mortality (0.663, 0.486 - 0.905), while most cytopenia/infection and VTE outcomes were similar with either therapy. Polyneuropathy and mood disorder diagnoses were higher with GLP-1RA versus SGLT2i (1.272, 1.052 - 1.539; 1.241, 1.008 - 1.528). CKD and stroke were not significantly different with either therapy. Conclusions: In this propensity-matched real-world cohort of anthracycline-treated women with breast cancer and diabetes, both GLP-1RA and SGLT2i were associated with improved survival and fewer cytopenias, infections, and VTE versus no exposure. Compared with SGLT2i, GLP-1RA showed more favorable cardio-renal and survival outcomes, whereas SGLT2i was associated with fewer polyneuropathy and mood disorder diagnoses. Prospective validation is needed.