Renal outcomes associated with sodium–glucose cotransporter 2 inhibitor use in kidney transplant recipients with type 2 or posttransplant diabetes

Abstract

Posttransplant diabetes mellitus (PTDM) increases the risk of graft failure and mortality. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) improve cardiovascular and renal outcomes in type 2 diabetes mellitus (T2DM), but evidence in kidney transplant recipients (KTRs) with T2DM or PTDM remains limited. We conducted a retrospective cohort study including adult KTRs with pretransplant T2DM or PTDM. Exposure was defined as continuous SGLT2i use for ≥90 days. The primary outcome was a composite of graft loss, all-cause mortality, or a ≥2-fold increase in serum creatinine relative to the week-4 posttransplant value occurring >3 months after baseline. Secondary outcomes included longitudinal changes in HbA1c, estimated glomerular filtration rate (eGFR), and urine protein-to-creatinine ratio (UPCR), as well as adverse events (acute kidney injury [AKI] and urinary/genital infections). Propensity score overlap weighting was used to balance baseline covariates, and time-to-event analyses were performed using an overlap-weighted Cox regression model. A total of 185 patients were included (116 SGLT2i users and 69 non-users), with a mean follow-up of 121 months. The primary composite outcome occurred less frequently in the SGLT2i group (P < .001). In an overlap-weighted Cox regression model, SGLT2i use was associated with a lower hazard of the composite endpoint (HR 0.30, 95% CI: 0.17–0.55; P < .001). Safety outcomes did not differ significantly between groups, including urinary sepsis/hospitalization categories, ketoacidosis, and genital infections. Among KTRs with T2DM or PTDM, SGLT2i use was associated with a lower combined risk of graft loss, all-cause mortality, or doubling of serum creatinine, without an increased incidence of adverse events.