Risk of Urogenital Infections in People With Type 2 Diabetes Initiating SGLT2is Versus GLP-1RAs in Routine Clinical Care: A Danish Cohort Study

OBJECTIVE: Anticipated risks of urinary tract infections (UTI) and genital tract infections (GTI) associated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) may prevent their use in clinical practice. We investigated whether initiation of SGLT2is, compared with glucagon-like peptide 1 receptor agonists (GLP-1RAs), was associated with an elevated risk of UTI and GTI in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: In this cohort study emulating a target trial, we included all adult metformin users initiating SGLT2is or GLP-1RAs in Denmark in 2016-2021 and used inverse-probability of treatment (IPT) weighting to balance potential confounders. We estimated IPT-weighted risk and risk ratios of community- or hospital-treated UTI and GTI, performing both intention-to-treat and on-treatment analyses. RESULTS: This study included 52,414 SGLT2i initiators and 27,023 GLP-1RA initiators with a median follow-up of 2.9 to 3.9 years. The estimated risks of UTI within the first year were nearly identical: 10.0% for SGLT2is and 10.2% for GLP-1RAs in intention-to-treat analyses corresponding to a risk ratio of 0.98 (95% CI 0.94, 1.03). For GTI, the 1-year risks were elevated under SGLT2i therapy at 2.0% vs. 0.7% (risk ratio 2.95 [95% CI 2.52, 3.44]). During the 5-year follow-up, the relative UTI risk remained almost constant (0.96 [95% CI 0.94, 0.99]) whereas the GTI risk ratio with SGLT2is decreased to 1.64 (95% CI 1.49, 1.80). CONCLUSIONS: In routine clinical care, SGLT2i initiation is not associated with increased risk of UTI compared with GLP-1RA initiation. However, early GTI risk is up to threefold larger in SGLT2i users.