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Risk of Phimosis Associated With SGLT2i Versus GLP-1RA: A Danish Cohort Study
Christine Ljungberg1, Mette Nørgaard1, Christina Vandenbroucke-Grauls1,2
1Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark.
Diabetes Care
|July 30, 2025
Summary
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) nearly double the risk of phimosis in men with type 2 diabetes compared to glucagon-like peptide-1 receptor agonists (GLP-1RA). This elevated risk persists over 8 years of follow-up.
Area of Science:
- Endocrinology
- Urology
- Pharmacology
Background:
- Type 2 diabetes management often involves medications with varying side effect profiles.
- Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are known to induce glucosuria, potentially altering the local microenvironment.
- Phimosis, a condition affecting the foreskin, has been anecdotally linked to SGLT2i use.
Purpose of the Study:
- To investigate the association between initiating SGLT2 inhibitors versus glucagon-like peptide-1 receptor agonists and the risk of developing phimosis in adult males with type 2 diabetes.
- To quantify the comparative risk of phimosis between these two common classes of diabetes medications.
Main Methods:
- A population-based, active-comparator new-user cohort study was conducted using Danish medical databases.
- Adult male metformin users initiating either SGLT2i or GLP-1RA between 2016 and 2021 were included.
- Inverse probability of treatment weighting was employed to balance confounders, and intention-to-treat risk and risk ratios were calculated.
Main Results:
- The study included 32,486 SGLT2i initiators and 14,793 GLP-1RA initiators, with a median follow-up of 4 years (up to 8 years).
- The 1-year risk of phimosis was 0.9% for SGLT2i users versus 0.5% for GLP-1RA users, yielding a risk ratio of 1.88 (95% CI, 1.43 to 2.47).
- Over 8 years, the cumulative risk of phimosis reached 4.8% for SGLT2i users and 3.6% for GLP-1RA users (risk ratio, 1.36; 95% CI, 1.14 to 1.61).
Conclusions:
- Sodium-glucose cotransporter 2 inhibitor use is associated with a significantly increased risk of phimosis in men with type 2 diabetes compared to GLP-1RA use.
- The risk of phimosis associated with SGLT2i initiation is nearly twofold higher within the first year and remains elevated over an 8-year follow-up period.
- These findings highlight a potential urological risk associated with SGLT2i therapy that warrants consideration in clinical practice.
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