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. 2025 Sep 2;8(9):e2534485.
doi: 10.1001/jamanetworkopen.2025.34485.

SGLT2 Inhibitors and External Genital Infection in Male Patients With Type 2 Diabetes

Tsung-Han Cheng  1 , Kun-Che Lin  2 , Albert Tzu-Ming Chuang  3   4 , Michael Chun-Yuan Cheng  3   4 , Shih-Chieh Shao  3   4   5 , Swu-Jane Lin  6 , Tsung-Yen Lin  2   7 , Yuh-Shyan Tsai  2 , Edward Chia-Cheng Lai  3   4 , Che-Yuan Hu  2   8 , Kuan-Yu Wu  2
Affiliations

SGLT2 Inhibitors and External Genital Infection in Male Patients With Type 2 Diabetes

Tsung-Han Cheng et al. JAMA Netw Open. .

Abstract

Importance: New medications for type 2 diabetes (T2D) control, such as sodium-glucose cotransporter-2 inhibitors (SGLT2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs), have emerged. However, the US Food and Drug Administration has warned about potential risks of Fournier gangrene, a severe genital infection associated with SGLT2I use.

Objective: To determine comparative risks of male external genital infections (MEGIs) in adult male patients with T2D treated with SGLT2Is.

Design, setting, and participants: A population-based cohort study analyzing Taiwan's National Health Insurance Research Database was conducted to evaluate the MEGI risk in adult male patients with T2D newly treated with SGLT2Is between January 1, 2009, and December 31, 2020. Patients newly treated with GLP-1RAs were chosen during the same period for the active-comparator group, and propensity scores with inverse probability of treatment weighting were applied to balance the baseline characteristics between the 2 treatment groups. Data analyses were conducted between February 2023 and April 2025.

Exposures: Treatment with SGLT2Is or GLP-1RAs.

Main outcomes and measures: The primary outcome was the incidence of MEGI, identified using International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes. To examine the result consistency, subgroup analyses based on age (older or younger than 60 years), diabetes severity (insulin use or not), and kidney function were conducted.

Results: The study included 239 757 patients; 224 360 initiated SGLT2Is (mean [SD] age, 58.4 [12.3] years) and 15 397 initiated GLP-1RAs (mean [SD] age, 58.1 [13.6] years). Compared with the GLP-1RA group, the SGLT2I group had a significantly increased risk of MEGI (hazard ratio [HR], 1.65; 95% CI, 1.59-1.71). The subgroup analyses indicated an increased risk of MEGI in the SGLT2I group among patients younger than 60 years (HR, 2.04; 95% CI, 1.58-2.65), those with an estimated glomerular filtration rate of 60 mL/min/1.73 m2 (HR, 1.69; 95% CI, 1.34-2.15), and those with hemoglobin A1c below 7% (HR, 3.22; 95% CI, 1.71-6.03).

Conclusions and relevance: These findings suggest that SGLT2Is are associated with a higher risk of MEGI in adult male patients with T2D, compared with GLP-1RAs. Clinicians should be cautious when prescribing SGLT2Is in male patients with T2D.

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Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure.
Figure.. Cumulative Incidence of Male External Genital Infections for SGLT2Is and GLP-1RAs After Inverse Probability of Treatment Weighting
Abbreviations: GLP-1RAs, glucagon-like peptide-1 receptor agonists; SGLT2Is, sodium-glucose cotransporter-2 inhibitors.
See this image and copyright information in PMC

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