Early safety observations of peri-transplant SGLT2 inhibitor use in lung transplant recipients.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) provide cardiovascular and renal benefits in non-transplant populations, but their safety in lung transplant recipients remains poorly defined, particularly during the peri-transplant period. We evaluated early postoperative complications, long-term allograft outcomes, and adverse events associated with SGLT2i exposure before transplantation or within the first 90 days after lung transplantation (LTx). We performed a single-center retrospective cohort study of 443 adult recipients who underwent primary isolated LTx at Northwestern University between January 2018 and May 2024. Patients were classified according to peri-transplant SGLT2i exposure, defined as either ongoing use at the time of transplantation or de novo initiation within 90 days after transplantation. Early outcomes included primary graft dysfunction (PGD) grade 3 at 72 hours and major postoperative complications. Long-term outcomes included chronic lung allograft dysfunction (CLAD) and overall survival. Time-to-event analyses for CLAD and survival used a postoperative day-90 landmark. Multivariable logistic and Cox regression analyses were performed. Among 443 recipients, 11 (2.5%) were exposed to SGLT2i either before transplantation or within 90 days after transplantation; 7 were receiving SGLT2i at the time of transplant and 4 initiated therapy 
de novo within 90 days post-transplant. Pre-transplant SGLT2i use was not associated with increased early postoperative complications or PGD grade 3. Among the small number of exposed patients, no clear excess in early complications, CLAD, or death was observed. Among SGLT2i-exposed patients, 10 of 11 continued therapy without interruption. No cardiovascular deaths or genitourinary infections were observed during follow-up. One patient developed diabetic ketoacidosis (DKA) 27 months after transplantation, leading to permanent drug discontinuation. In this single-center cohort, peri-transplant SGLT2i exposure was uncommon but was not associated with worse early graft outcomes, CLAD, or survival among treated patients. These findings suggest a reassuring early safety and feasibility signal for carefully selected lung transplant recipients and support the need for larger multicenter studies.