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

C. Ljungberg, F. Kristensen, M. Dalager-Pedersen, Christina Vandenbroucke-Grauls, H. T. Sørensen, Mette Nørgaard, R. Thomsen

Diabetes Care, 2025

17 citations

Abstract

OBJECTIVE

Anticipated risks of urinary tract infections (UTI) and genital tract infections (GTI) associated with sodium-glucose cotransporter 2 inhibitors (SGLT2i) may prevent their use in clinical practice. We investigated whether initiation of SGLT2i, 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 SGLT2i 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 SGLT2i and 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% 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…

How strong is the evidence?

Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.

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