Emerging Effects of Glucagon‐Like Peptide‐1 Receptor Agonists and Sodium‐Glucose Cotransporter 2 Inhibitors on Male Sexual Hormones and Behaviors: Systematic Review and Meta‐Analysis

BACKGROUND: The efficacy of glucagon-like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) in weight loss and long-term cardiovascular (CV) safety is established. The role of these medications on male sexual hormones and function has not been adequately clarified. OBJECTIVE: To systematically review and meta-analyze the effects of GLP1-RA and SGLT2i on obesity-associated hypogonadism and sexual dysfunctions. METHODS: A systematic search of Medline was conducted from 1969 to August 2025, according to PRISMA and MOOSE guidelines. All observational or randomized controlled trials evaluating the effects of GLP1-RA or SGLT2i on hormonal and/or sexual parameters in overweight and obese subjects with or without diabetes mellitus (DM) were included in the analysis. RESULTS: Eight studies, including 375 subjects, evaluated the effects of GLP1-RAs, whereas three, accounting for 52 subjects, investigated the effects of SGLT2is. Both classes of medications showed an overall improvement of body composition and metabolic profile, resulting in positive erectile function outcomes. Only GLP1-RAs significantly increased total and calculated free testosterone along with gonadotropins. The findings of GLP1-RAs on T levels were independent from the observed weight loss, suggesting a direct, rather than an indirect, mechanism of action on the hypothalamus-pituitary-testis axis. Finally, the use of testosterone replacement therapy (TRT) showed better results as compared to GLP1-RAs when orgasm and sexual satisfaction domains were investigated. CONCLUSIONS: Present data support the use of GLP1-RAs for improving sexual dysfunction, and its underlying CV problems, in obese patients with ED. A combination of TRT and GLP1-RAs can be considered in selected cases. Data on SGLT2is are too limited to draw final conclusions.