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

🥇 Top 1% JournalApr 2, 2025Diabetes care

Risk of Urinary and Genital Infections in People with Type 2 Diabetes Starting SGLT2 Inhibitors Compared to GLP-1 Receptor Agonists in Everyday Care

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Abstract

Among 52,414 users, the 1-year risk of urinary tract infections (UTI) was 10.0% for sodium-glucose cotransporter 2 inhibitors (SGLT2is) and 10.2% for glucagon-like peptide 1 receptor agonists (GLP-1RAs).

The risk ratio for UTI between SGLT2is and GLP-1RAs was 0.98, indicating similar risk levels.
For genital tract infections (GTI), the 1-year risk was 2.0% for SGLT2is compared to 0.7% for GLP-1RAs, resulting in a risk ratio of 2.95.
Over a 5-year follow-up, the relative risk of UTI remained stable at 0.96.
In contrast, the risk ratio for GTI with SGLT2is decreased to 1.64 over the same period.
Initiation of SGLT2is is not associated with a higher risk of UTI compared to GLP-1RAs, but early GTI risk is significantly increased.

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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.

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