Risk of Urogenital Infections in People with Type 2 Diabetes Initiating SGLT2i versus GLP-1RA in Routine Clinical Care: A Danish Cohort Study

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posted on 2025-04-02, 16:04 authored by Christine Ljungberg, Frederik Pagh Bredahl Kristensen, Michael Dalager-Pedersen, Christina Vandenbroucke-Grauls, Henrik Toft Sørensen, Mette Nørgaard, Reimar Wernich Thomsen

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, as 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% in SGLT2is, 10.2% in 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% versus 0.7%, risk ratio 2.95 (95% CI 2.52, 3.44). During 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 as compared to GLP-1RA initiation. However, early GTI risk is up-to 3-fold larger in SGLT2i users.