Real-World Outcomes of SGLT2 Inhibitors in Kidney Transplant Recipients with Post-Transplant Diabetes Mellitus: An Effectiveness and Safety Analysis

• SGLT2i associated with stable graft function in transplant diabetes. • Weight, BP, and lipid reductions observed. • Renal safety profile favorable: eGFR stable, no proteinuria rise. • UTI most common adverse event; no euglycemic ketoacidosis. • Real-world data suggest safe use post-transplant. Sodium–glucose cotransporter-2 inhibitors (SGLT2i) are key cardiorenal agents, yet their safety and efficacy in kidney transplant recipients (KTRs) with post-transplant diabetes mellitus (PTDM) remain insufficiently characterized. To evaluate the renal safety, tolerability, and cardiometabolic profile associated with SGLT2 inhibitor use in this population. This single-center retrospective cohort screened 183 KTRs prescribed GLP-1 receptor agonists and/or SGLT2i (August 2013–April 2024). After applying prespecified exclusion criteria, 65 kidney transplant recipients with PTDM receiving SGLT2i for >3 months were included (mean treatment duration 2.56 ± 1.37 years). Primary outcomes were renal safety (annualized eGFR slope and uPCR/uACR). Secondary outcomes included cardiometabolic/hemodynamic measures and adverse events. Allograft function was stable, with an annualized eGFR slope of +1.35 mL/min/1.73 m²/year (95% CI: –0.49 to +3.19; p = 0.148). Proteinuria markers (uPCR, uACR) showed no significant increase. Serum urea rose (70.00 ± 25.80 to 75.30 ± 33.86 mg/dL, p = 0.003), while serum creatinine and cystatin C were unchanged. Body weight decreased by 3.02 kg (p = 0.001) and BMI by 1.24 kg/m² (p < 0.001). Systolic and diastolic blood pressure were lower by 7.0 and 4.9 mmHg, respectively (both p < 0.001). Reductions were observed in total cholesterol (172.60 ± 33.60 to 158.90 ± 37.70 mg/dL, p = 0.001) and LDL-cholesterol (87.60 ± 36.20 to 75.80 ± 33.60 mg/dL, p = 0.001). Serum uric acid decreased from 6.56 ± 1.56 to 6.24 ± 1.65 mg/dL (p = 0.021). Electrolytes were stable. Urinary tract infections occurred in 15.4% (predominantly asymptomatic). No cases of euglycemic diabetic ketoacidosis, allograft rejection, or genital infections were observed. In KTRs with PTDM, intermediate-term SGLT2i therapy was associated with preserved allograft function, cardiometabolic benefits, and a favorable safety profile. These real-world data describe a clinical profile supporting further investigation and provide rationale for prospective trials.