Risk of Phimosis Associated With SGLT2i Versus GLP-1RA: A Danish Cohort Study

Abstract

OBJECTIVE Sodium-glucose cotransporter 2 inhibitors (SGLT2i) induce glucosuria, potentially leading to infection and inflammation in the preputial microenvironment, subsequently increasing the risk of phimosis. We aimed to investigate the risks of phimosis in males with type 2 diabetes initiating SGLT2i or glucagon-like peptide-1 receptor agonists (GLP-1RA). RESEARCH DESIGN AND METHODS In this population-based active-comparator new-user cohort study emulating a target trial, we included all adult male metformin users in Denmark initiating SGLT2i or GLP-1RA between 2016 and 2021. We used inverse probability of treatment weighting to balance the distribution of potential confounders. We estimated weighted intention-to-treat risk and risk ratios of phimosis identified from population-based medical databases. RESULTS In this study, we included 32,486 SGLT2i initiators and 14,793 GLP-1RA initiators with a median follow-up of 4 years (maximum 8 years). The risk of phimosis was elevated among SGLT2i users. The 1-year risk of phimosis was 0.9% among new SGLT2i users and 0.5% among new GLP-1RA users, corresponding to a 1-year risk ratio of 1.88 (95% CI, 1.43 to 2.47). During 8 years of follow-up, the risk of phimosis accumulated up to 4.8% in SGLT2i users and 3.6% in GLP-1RA users, with an 8-year risk ratio of 1.36 (95% CI, 1.14 to 1.61). CONCLUSIONS SGLT2i use was associated with a nearly twofold increased phimosis risk 1 year after treatment initiation in men with type 2 diabetes, compared with GLP-1RA use. Over 8 years of follow-up, the risk remained elevated, indicating a persistently higher risk associated with SGLT2i use.