Do the treatment selection factors emphasized in clinical guidelines—Chronic kidney disease, cardiovascular disease, and heart failure—contribute to the risk of urinary tract infections during the administration of sodium‐glucose cotransporter‐2 inhibitors?

ABSTRACT Aims/Introduction Sodium‐glucose cotransporter‐2 inhibitors (SGLT2Is) are recommended in Japan for patients with cardiovascular disease (CVD), heart failure (HF), or chronic kidney disease (CKD) due to their organ‐protective effects, leading to increased use in high‐risk populations. However, whether urinary tract infection (UTI) risk associated with SGLT2Is differs according to the presence of these factors remains unclear. This study aimed to estimate UTI risk among SGLT2I users and treatment selection factors and examine whether these factors modify risk. We selected dipeptidyl peptidase‐4 inhibitors (DPP4Is) as the comparators. Materials and Methods This retrospective cohort study used DeSC claims data from patients with diabetes mellitus who received their first prescription for either an SGLT2I or a DPP4I between October 2014 and February 2023. The analysis focused on data from 2019 to 2022. Hazard ratios (HRs) for UTI incidence were estimated using Cox proportional hazard regression. Results A total of 66,968 SGLT2I users and 170,678 DPP4I users were aged 65 years or older. UTI incidence among SGLT2I users was 2.04% in those with treatment selection factors and 0.84% in those without. Compared with DPP4I users, the HR for UTI was 0.80 in patients with treatment selection factors and 0.51 in those without treatment selection factors. Conclusions SGLT2I use was not associated with an increase in UTI risk, regardless of treatment selection factor status. These findings suggest a favorable safety profile for SGLT2Is even among high‐risk populations, supporting their use following clinical guidelines.