SGLT2 Inhibitors and Clinical Outcomes in Kidney Transplant Recipients with Diabetes: A Real-World Cohort Analysis

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are widely used in diabetic patients for cardiovascular and renal protection. However, their safety and effectiveness in kidney transplant (KT) recipients with diabetes remain unclear. We evaluated the impact of SGLT2 inhibitor use on clinical outcomes in diabetic KT recipients using real-world data. Methods: We performed a retrospective cohort analysis using the TriNetX Global Collaborative Network. Adult KT recipients with type 2 diabetes were categorized based on post-transplant SGLT2 inhibitor use. Cohort A (n=10,377) included patients on SGLT2 inhibitors (empagliflozin, dapagliflozin, or canagliflozin), while Cohort B (n=95,150) included those not on these agents. Outcomes were assessed over a 5-year period and included mortality, graft failure, dialysis dependence, proteinuria, myocardial infarction (MI), stroke, urinary tract infection (UTI), pyelonephritis, and amputation. Risk ratios (RR) and hazard ratios (HR) were calculated. Results: SGLT2 inhibitor use was associated with significantly lower mortality (8.2% vs. 15.9%; HR: 0.82; 95% CI: 0.77–0.88; p<0.001) and lower risk of graft failure (11.0% vs. 25.8%; HR: 0.47; 95% CI: 0.45–0.50; p<0.001). Dialysis dependence was also reduced (42.1% vs. 56.8%; HR: 0.72; p<0.001). SGLT2 users had modestly lower rates of MI (7.5% vs. 8.3%; RR: 0.90; p=0.004), stroke (5.6% vs. 6.4%; RR: 0.89; p=0.004), and UTI (9.0% vs. 9.9%; RR: 0.91; p=0.004). Pyelonephritis risk was also reduced (2.2% vs. 3.2%; RR: 0.69; p<0.001). There was no significant difference in amputation risk (1.9% vs. 2.0%; p=0.50). Proteinuria risk was slightly lower in SGLT2 users (24.8% vs. 26.1%; RR: 0.95; p=0.006), although survival analysis showed a modest increase in recurrence over time (HR: 1.20). Conclusion: Among diabetic kidney transplant recipients, SGLT2 inhibitor use was associated with improved graft and patient survival, reduced dialysis dependence, and favorable cardiovascular and infectious outcomes. These findings support the safe use of SGLT2 inhibitors in this population and highlight the need for prospective studies.