Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Post-Transurethral Resection of Bladder Tumor Infection and Prognosis

<b>Background/Objectives:</b> Sodium-glucose cotransporter-2 inhibitors (SGLT2is), by elevating urinary glucose levels, may predispose patients to urinary tract infections (UTI). However, limited evidence is available regarding the association between SGLT2is and postoperative outcomes after transurethral resection of bladder tumors (TURBT). We evaluated the impact of SGLT2is on post-TURBT pyuria and febrile UTI (fUTI), as well as oncological outcomes. <b>Methods:</b> We retrospectively reviewed the data of 812 patients with and without diabetes mellitus (DM) who underwent TURBT between January 2019 and May 2024. The patients were categorized into three groups: non-DM (Nara Medical University cohort, <i>n</i> = 344), DM non-SGLT2i (multi-institutional cohort, <i>n</i> = 363), and DM SGLT2i (multi-institutional cohort, <i>n</i> = 105). We compared fUTI-free survival, fUTI-related hospitalization-free survival, and persistent pyuria duration as well as oncological outcomes using the inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier method and Cox regression analysis. <b>Results:</b> No significant differences in fUTI-free or hospitalization-free survival were observed between the non-DM and DM groups, whereas the DM group had prolonged pyuria compared to the non-DM group (1-year pyuria rate: 36.6% vs. 18.2%; <i>p</i> < 0.001). In contrast, the DM SGLT2i group had significantly shorter fUTI-free survival (1-year fUTI-free survival: 83.0% vs. 90.0%; <i>p</i> = 0.013) and longer pyuria persistence (1-year pyuria rate: 70.6% vs. 28.9%; <i>p</i> < 0.001) than the DM non-SGLT2i group. Additionally, the DM SGLT2i group was significantly associated with shorter UTUC-free survival than the DM non-SGLT2i group (<i>p</i> = 0.0072). SGLT2i was an independent prognostic factor for fUTI and prolonged pyuria in IPTW-adjusted Cox regression analysis. No significant differences were observed in fUTI-free survival, hospitalization-free survival, or persistent pyuria duration among the different SGLT2i types. <b>Conclusions:</b> Temporal discontinuation of SGLT2i in the peri-TURBT period may prevent persistent postoperative pyuria and the risk of fUTI.