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Introduction: Endourological management of upper urinary tract stones has increased substantially, with ureteroscopy (URS) and percutaneous nephrolithotomy (PNL) now representing standard treatment modalities. Concurrently, the prevalence of type 2 diabetes mellitus (T2DM) and the use of sodium-glucose cotransporter 2 inhibitors (SGLT2is) are rising. While SGLT2is provide established cardiovascular and renal benefits, their impact on perioperative outcomes in endourological stone surgery remains unclear. Methods: In this retrospective single-centre cohort study, all patients undergoing URS, PNL, or endoscopic combined intrarenal surgery between January 2024 and February 2025 were included. Patients were stratified into non-diabetic controls (n = 150), T2DM without SGLT2i (n = 49), and T2DM with SGLT2i (n = 48). Outcomes included in-hospital complications (Clavien-Dindo), postoperative urinary tract infection (UTI)/urosepsis, and UTIs within 4 weeks after discharge. Multivariable logistic regression adjusted for age, BMI, comorbidity, preoperative urine culture, operative time, and procedure type. Results: Overall in-hospital complication rates were significantly higher in SGLT2i-treated patients, driven predominantly by minor, noninfectious events, while infectious outcomes remained comparable between groups. In multivariable analysis, SGLT2i therapy independently predicted in-hospital complications (p = 0.026). Preoperative urine culture status was the only independent predictor of postoperative UTI (p = 0.011). Conclusion: SGLT2i therapy in patients with T2DM undergoing endourological stone surgery was associated with increased minor in-hospital complications but not with higher perioperative infectious risk. Preoperative urine culture status remained the key determinant of postoperative UTI. Prospective multicentre studies are warranted to confirm these findings and optimize perioperative risk stratification in diabetic stone patients.

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