Risk of urinary tract infection with <scp>SGLT2</scp> inhibitor initiation in patients with immune‐mediated inflammatory diseases and type 2 diabetes: A target trial emulation using a Japanese hospital‐based claims database

AIMS/INTRODUCTION: To evaluate whether sodium-glucose cotransporter 2 inhibitor (SGLT2i) initiation is associated with the risk of urinary tract infection (UTI), with upper UTI and genital infection assessed as secondary outcomes, compared with metformin in patients with immune-mediated inflammatory diseases (IMIDs) and type 2 diabetes. MATERIALS AND METHODS: We conducted a target trial emulation using an active-comparator, new-user design with a Japanese hospital-based claims database from 2014 to 2024. Adults with IMIDs and type 2 diabetes who newly initiated an SGLT2i or metformin were included. The primary outcome was UTI; secondary outcomes were upper UTI and genital infection. Hazard ratios (HRs) were estimated using inverse probability of treatment weighting and weighted Cox proportional hazards models. Prespecified subgroup and interaction analyses further evaluated heterogeneity in UTI risk according to concomitant immunosuppressive therapies. RESULTS: We analyzed 1,845 SGLT2i initiators and 1,499 metformin initiators (mean age 71.8 years; 55.4% female). Compared with metformin initiation, SGLT2i initiation was not associated with increased risks of UTI (HR 1.14, 95% confidence interval [CI] 0.84-1.55) or upper UTI (HR 1.28, 95% CI 0.71-2.31). Results for UTI were broadly similar across categories of concomitant immunosuppressive therapies, and interaction analyses showed no evidence of effect modification across these strata, including glucocorticoid dose. The risk of genital infection was higher with SGLT2i initiation (HR 2.31, 95% CI 1.16-4.63). CONCLUSIONS: Among patients with IMIDs and type 2 diabetes, SGLT2i initiation was not associated with increased risks of UTI or upper UTI compared with metformin, although the risk of genital infection was higher.