From molecules to the clinic-pathophysiology of sodium-glucose cotransporter 2 inhibitors and their emerging role in urology: A comprehensive review from the European Association of Urology Section of Endourology.

OBJECTIVE: This review aims to comprehensively evaluate the mechanisms of action of sodium-glucose cotransporter 2 inhibitors (SGLT2is), with a specific focus on their relevance to urological practice, including both potential benefits and risks. METHODS: A systematic literature search was conducted in February 2025 using PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and Google Scholar. Studies addressing the pharmacodynamics of flozins, their systemic effects, and genitourinary outcomes were included. Data were organized into mechanistic themes: tubular glucose and sodium transport, organ protection, antioxidative signaling, and potential anticancer activity. Urological effects were analyzed separately for non-oncological and oncological domains, and adverse outcomes were summarized. RESULTS: SGLT2is exert beneficial effects beyond glycemic control, including reduced intraglomerular pressure, improved endothelial function, antioxidative and anti-inflammatory activities, and modulation of cellular metabolism and proliferation. These effects translate to potential benefits in erectile dysfunction, nephrolithiasis, benign prostatic hyperplasia, and possibly genitourinary malignancies. However, flozins are associated with risks including genital mycotic infections, euglycemic ketoacidosis, and, in rare cases, severe urinary tract infections. Conflicting data exist regarding the actual risk of UTIs, with recent evidence suggesting a lower or neutral risk when used appropriately. CONCLUSION: Flozins represent a promising therapeutic class with multifaceted benefits that extend into the field of urology. However, individualized risk assessment remains essential, and further urology-focused clinical research is needed to clarify their full utility and safety in this domain.