SGLT2 inhibitors and cardiovascular outcomes in patients with diabetes following hematopoietic stem cell transplantation: A propensity-matched cohort study

Background: Hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of cardiovascular disease, and diabetes mellitus (DM) is common after transplantation. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated cardioprotective effects in diabetic populations, but their impact in HSCT recipients is unclear. We evaluated cardiovascular outcomes associated with SGLT2i use in diabetic HSCT patients. Methods: Using the TriNetX federated research network, we conducted a retrospective cohort study of patients with DM who underwent HSCT between 2014 and 2019. Patients were stratified by SGLT2i exposure. Outcomes were assessed from 100 days post-HSCT through 5 years. Primary endpoints included all-cause mortality, hospitalization, myocardial infarction, atrial fibrillation, and heart failure exacerbation. Propensity score matching (1:1) balanced baseline characteristics. Results: Among 11,682 diabetic HSCT patients, 1446 (12.4%) received SGLT2i. After matching (n = 1308 per group), SGLT2i use was associated with significantly lower all-cause mortality at 1 year (OR 0.54, 95% CI 0.41–0.71), 3 years (OR 0.56, 95% CI 0.45–0.69), and 5 years (OR 0.49, 95% CI 0.40–0.60; all p < 0.001). At 5 years, SGLT2i use was also associated with reduced hospitalization (OR 0.76, 95% CI 0.65–0.89; p < 0.001) and heart failure exacerbation (OR 0.80, 95% CI 0.68–0.95; p = 0.009). No significant differences were observed in myocardial infarction or atrial fibrillation. Findings were consistent across transplant types. Conclusion: SGLT2i use was associated with reduced mortality, hospitalization, and heart failure events in diabetic HSCT recipients, with associations evident early and sustained through 5 years. Prospective studies are warranted.