Background Existing evidence on urogenital infection risk associated with sodium-glucose co-transporter 2 (SGLT2) inhibitors is primarily based on trials of individual agents compared to placebo or other antidiabetic medications. Therefore, the comparative safety of individual SGLT2 inhibitors on urogenital infection remains unclear.

Objective To evaluate the comparative safety of two commonly used SGLT2 inhibitors (dapagliflozin, empagliflozin) on urogenital infection.

Methods In this target trial emulation study, we identified patients with type 2 diabetes (T2D) initiating dapagliflozin or empagliflozin in 2016-2023 using the National Health Insurance Service database of South Korea. The study outcomes were urinary tract infection (UTI) and genital tract infection (GTI). They were followed from the date of study drug initiation until the earliest of outcome, initial drug discontinuation or switching, death, or study end date (per-protocol approach). We used 1:1 propensity score matching to balance covariates between groups. Incidence rates per 100 person-years (IRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) of UTI and GTI were estimated using Poisson regressions and Cox proportional hazard models, respectively. Subgroup analysis stratified by age, sex, baseline insulin use, duration of T2D (< 5 years, ≥ 5 years), chronic kidney disease, previous UTI or GTI, and SGLT2 inhibitors dosage (i.e., dapagliflozin 5mg or empagliflozin 10 mg as low dose and dapagliflozin 10 mg or empagliflozin 25mg as high dose).

Results This study included 995,131 dapagliflozin initiators (mean age 58.7 years, male 61.2%) and 617,509 empagliflozin initiators (mean age 58.9 years, male 60.7%), with similar baseline characteristics before matching. After matching, during a mean follow-up of 1.4 years, IRs for UTI were 6.61 (95% CI, 6.55–6.66) in dapagliflozin users and 6.60 (6.54–6.65) in empagliflozin users per 100 person-years; IRs for GTI were 5.65 (95% CI, 5.61–5.70) for dapagliflozin users and 5.76 (95% CI, 5.71–5.81) in empagliflozin users. Compared to empagliflozin use, dapagliflozin use was not associated with UTI (HR 1.00, 95% CI, 0.99–1.01) and GTI (HR 0.99, 95% CI, 0.97–1.00) risks. These findings were highly consistent in predefined subgroup analyses.

Conclusions In this nationwide, population-based cohort study, dapagliflozin and empagliflozin had comparable risks of UTI and GTI among patients with T2D.