Effects of empagliflozin on reproductive system in men without diabetes

• Published in: Scientific reports Vol. 14; no. 1; pp. 13802 - 4
• Main Authors: Kosinski, Christophe, Papadakis, Georgios E., Salamin, Olivier, Kuuranne, Tiia, Nicoli, Raul, Pitteloud, Nelly, Zanchi, Anne
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.06.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 692/163; 692/163/2743/2730; 692/308/2779/109; Adult; Androgens; Androgens - metabolism; Benzhydryl Compounds - pharmacology; Beta cells; Congestive heart failure; Diabetes; Diabetes mellitus (non-insulin dependent); Double-Blind Method; Empagliflozin; Glucosides - pharmacology; Gonadotropins; Heart diseases; Hormones; Humanities and Social Sciences; Humans; Inhibin; Inhibins - blood; Inhibins - metabolism; Leydig cells; Leydig Cells - drug effects; Leydig Cells - metabolism; Male; Males; Middle Aged; multidisciplinary; Pituitary; Pituitary (anterior); Placebos; Renal cortex; Reproductive system; Science; Science (multidisciplinary); Sertoli cells; Sertoli Cells - drug effects; Sertoli Cells - metabolism; SGLT2 inhibitors; Sodium-glucose cotransporter; Sodium-Glucose Transporter 2 - metabolism; Sodium-Glucose Transporter 2 Inhibitors - pharmacology; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use; Spermatogenesis; Steroid hormones; Testis - drug effects; Testis - metabolism; Testosterone; Testosterone - blood; Empagliflozin; Testosterone; Reproductive system; SGLT2 inhibitors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-64684-3

Sodium-glucose cotransporter (SGLT) 2 inhibition is a well-known target for the treatment of type 2 diabetes, renal disease and chronic heart failure. The protein SGLT2 is encoded by SLC5A2 (Solute Carrier Family 5 Member 2), which is highly expressed in renal cortex, but also in the testes where glucose uptake may be essential for spermatogenesis and androgen synthesis. We postulated that in healthy males, SGLT2 inhibitor therapy may affect gonadal function. We examined the impact on gonadal and steroid hormones in a post-hoc analysis of a double-blind, randomized, placebo-controlled research including 26 healthy males who were given either placebo or empagliflozin 10 mg once daily for four weeks. After one month of empagliflozin, there were no discernible changes in androgen, pituitary gonadotropin hormones, or inhibin B. Regardless of BMI category, the administration of empagliflozin, a highly selective SGLT2 inhibitor, did not alter serum androgen levels in men without diabetes. While SGLT2 is present in the testes, its inhibition does not seem to affect testosterone production in Leydig cells nor inhibin B secretion by the Sertoli cells.