Comparing the effects of SGLT2i versus DPP4i on cardiovascular outcomes in breast cancer patients with aromatase inhibitors

Background Aromatase inhibitors (AIs) are associated with improved cancer-related survival in breast cancer, but also higher risks of adverse cardiovascular outcomes. This study compared cardiovascular outcomes between sodium-glucose cotransporter-2 inhibitor (SGLT2i) and dipeptidyl peptidase-4 inhibitor (DPP4i) among breast cancer patients receiving AIs. Methods This was a retrospective, territory-wide study enrolling female patients ≥45 years old with diabetes mellitus and breast cancer who received SGLT2i or DPP4i on the date of AIs initiation, between 2015 and 2020 in Hong Kong. The primary outcome was major adverse cardiovascular events (MACE). The secondary outcomes included components of MACE [stroke/transient ischemic attack (TIA), nonfatal myocardial infarction (MI), and cardiovascular death], heart failure, and all-cause mortality. Multivariable Cox regression was applied to evaluate the association between SGLT2i versus DPP4i with outcomes. Results Initially, a total of 76 147 diabetes patients treated with SGLT2i or DPP4i were identified. After matching, 226 patients (mean age, 65.5 ± 7.6 years) were included (113 SGLT2i users versus 113 DPP4i users). During a median follow-up of 5.51 years, 43 (19.02%) patients developed composite MACE. Compared with DPP4i users, SGLT2i was not significantly associated with MACE [hazard ratio (HR): 0.54; 95% confidence interval (CI): 0.27–1.10] in the adjusted model. For the secondary outcomes, breast cancer patients treated with SGLT2i presented with an 84% lower risk of stroke/TIA (HR: 0.16; 95% CI: 0.04–0.61) than DPP4i users after adjustments. No significant associations were observed between SGLT2i with MI (HR: 0.41; 95% CI: 0.10–1.69), cardiovascular mortality (HR: 0.86; 95% CI: 0.20–3.70), all-cause mortality (0.51; 95% CI: 0.17–1.58), and heart failure (0.47; 95% CI: 0.12–1.89), in relation to DPP4i. Conclusion SGLT2i was associated with lower risks of stroke/TIA in diabetic patients with breast cancer receiving AIs compared with DPP4i.