Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are important anti-hyperglycemic medications with reno-protective benefits for patients with diabetic kidney disease. Their utilization in kidney transplant recipients (KTRs) remains underexplored due to safety concerns, particularly regarding urinary tract infections. This study investigates the safety profile of SGLT2i therapy in KTRs.

We conducted a retrospective analysis of KTRs with diabetes mellitus, comparing those treated with SGLT2i to those on standard diabetes therapy, monitored over three years at a tertiary center. The primary outcome was a renal composite of dialysis, re-transplantation, acute kidney failure, or acute rejection. Secondary outcomes included urinary tract infections, diabetic ulcers, fractures, amputations, diabetic ketoacidosis, all-cause mortality, and glycemic control.

Two hundred forty individuals using SGLT2i (median age 63, 20 % female) were matched with non-users. SGLT2i users had a lower incidence of the composite renal outcome (8.9 vs. 13.3 events per 100 patient-years), but after adjustment for independent predictors, the risk was similar (HR 0.99, 95 % CI 0.65–1.52, P = 0.970). Other outcomes showed comparable or lower risks in SGLT2i users. Glycemic control improved more significantly in SGLT2i users.

In KTRs with diabetes, SGLT2i therapy improved glycemic control without increased safety concerns compared to standard treatments. Both groups exhibited similar risks of significant kidney-related events and all-cause mortality. These findings provide crucial insights into the existing limited data concerning this vulnerable population, which faces elevated risks of renal complications and medication-related adverse effects. Ongoing randomized controlled trials will provide additional safety data for SGLT2i in KTRs.