Urogenital Infection Risk Associated With SGLT2 Inhibitors Versus DPP-4 Inhibitors in Type 2 Diabetes and Chronic Kidney Disease: A Nationwide Target Trial Emulation.

Although sodium-glucose cotransporter-2 inhibitors (SGLT2i) are recommended for patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), concerns regarding urogenital infections persist. Therefore, we evaluated the risk of urinary tract infection (UTI) and genital tract infection (GTI) after SGLT2i initiation in this population. Using nationwide Korean claims data, we emulated a target trial within an active-comparator, new-user cohort design. Adults with T2DM and CKD who initiated SGLT2i or dipeptidyl peptidase-4 inhibitors (DPP-4i) between 2016 and 2023 were included. After inverse probability of treatment weighting, Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). Among 41,801 eligible initiators, 6385 initiated SGLT2i and 35,416 initiated DPP-4i. Compared with DPP-4i initiation, SGLT2i initiation was not associated with increased UTI risk (HR, 0.99; 95% CI, 0.83-1.17); instead, it was associated with a modestly increased GTI risk (HR, 1.31; 95% CI, 1.09-1.58). Severe UTI and GTI requiring hospitalization or emergency department visits did not differ between groups. Moreover, the findings were robust across per-protocol analyses, Fine-Gray competing-risks models, propensity score matching, and alternative outcome definitions. Subgroup and landmark analyses showed no consistent increase in UTI risk, whereas excess GTI risk clustered early and was most pronounced among women aged 65-79 years. Overall, SGLT2i initiation was not associated with increased UTI risk and was associated with only a modest, early increase in GTI risk, without an increase in severe urogenital infections. These findings support clinically indicated use of SGLT2i with targeted early counseling, particularly in older women.