Sodium‐glucose cotransporter‐2 inhibitors and the risk of urinary tract infection among diabetic patients in Japan: Target trial emulation using a nationwide administrative claims database.

Aim: To assess the risk of urinary tract infection (UTI) occurrence associated with sodium‐glucose cotransporter‐2 (SGLT2) inhibitor use relative to biguanide use in diabetes in a population‐based cohort study using a target trial emulation framework. Methods: Using a Japanese nationwide administrative claims database, we constructed a cohort of patients aged ≥40 years who were dispensed SGLT2 inhibitors, dipeptidyl peptidase‐4 (DPP‐4) inhibitors or biguanides between April 2014 and March 2015. For computational ease, we randomly sampled 100% of SGLT2 inhibitor users, 3% of DPP‐4 inhibitor users, and 20% of biguanide users; new antidiabetic drug initiators were analysed. We estimated the intention‐to‐treat (ITT) hazard ratios (HRs) of UTI with inverse probability of treatment (IPT)‐weighted Coxʼs proportional hazards models that ignored subsequent treatment changes. Treatment weights were computed using patient sex, age, medications, medical history and hospitalization history. We also estimated per‐protocol (PP) HRs using IPT‐ and inverse probability of censoring‐weighted Coxʼs models that adjusted for nonrandom treatment changes. Results: We analysed 11 364 SGLT2 inhibitor initiators, 9035 DPP‐4 inhibitor initiators, and 10 359 biguanide initiators. When compared with biguanide initiators, SGLT2 inhibitor initiators had a crude HR of 1.14 (95% confidence interval [CI] 1.05‐1.24), an ITT HR of 0.94 (95% CI 0.86‐1.03), and a PP HR of 0.90 (95% CI 0.78‐1.03); and DPP‐4 inhibitor initiators had a crude HR of 1.13 (95% CI 1.04‐1.23), an ITT HR of 0.85 (95% CI 0.77‐0.94), and a PP HR of 0.83 (95% CI 0.71‐0.95). Conclusion: Use of SGLT2 inhibitors or DPP‐4 inhibitors did not increase the risk of UTI compared with biguanide use. Accounting for treatment changes did not substantially influence the estimated effects. [ABSTRACT FROM AUTHOR]