Risk of urinary tract infections associated with SGLT2 inhibitor use in patients with RA: a target trial emulation study

OBJECTIVES: This study aimed to describe annual trends in sodium-glucose cotransporter-2 inhibitor (SGLT2i) prescriptions among patients with RA and diabetes mellitus (DM), and to assess whether SGLT2i use increases urinary tract infection (UTI) risk, emulating a target trial. METHODS: An administrative claim database identified RA patients aged ≥18 years with type 2 DM from April 2015 to April 2023. Population 1 included RA patients with DM for assessing diabetes medication status. Population 2 included those with newly initiated first- or second-line antidiabetic medications. The primary outcome was UTI, defined using diagnostic code and antibiotic prescription. For intention-to-treat (ITT) analysis, we used quasi-Poisson regression, whereas for as-treated (AT) analysis, we applied Poisson mixed-effects models. RESULTS: Among the 26 754 patients in Population 1, SGLT2i prescriptions notably increased, while traditional diabetes medications decreased. Population 2 included 9772 patients (mean age 69.8 years, 60% women, 13% SGLT2i initiators, 42% on glucocorticoids). During a mean 34-month follow-up, 2269 UTI events occurred in 1373 patients. ITT analysis showed no significant difference between SGLT2i and other antidiabetic drug. However, AT analysis demonstrated statistically significant association (adjusted incidence rate ratio 1.64, 95% CI 1.26-2.13). The SGLT2i-daily glucocorticoid dose interaction was not significant in either model. CONCLUSIONS: Among RA patients with DM, SGLT2i use may inherently increase the risk of UTI compared with other antidiabetics. However, the ITT analysis findings support the safety of SGLT2i selection in routine clinical practice, including in patients receiving glucocorticoids.