(119) Exploring the Impact of GLP-1 Analogues on Libido and Sexual Function

Introduction Glucagon-like peptide-1 (GLP-1) analogues are established therapies for type 2 diabetes, obesity, and cardiovascular risk reduction, with expanding indications in metabolic and neuropsychiatric disease. Recent research highlights their impact on central reward pathways, implicating GLP-1 analogues in the modulation of addictive behaviors and substance use disorders. This is clinically relevant given the overlap between reward regulation, sexual function, and addiction. Objective To systematically review and synthesize clinical and pharmacovigilance data on the impact of GLP-1 analogues on libido and sexual function in adults, with attention to sex differences, hormonal effects, adverse event profiles and while explicitly connecting these effects to their role in reward neurobiology. Methods Methods included a literature review of randomized controlled trials, observational studies, and translational research published in the last five years, focusing on sexual desire, reproductive hormones, reward-related behaviors, and addiction endpoints in adults treated with GLP-1 analogues (semaglutide, dulaglutide, tirzepatide, exenatide, liraglutide, lixisenatide).Data extraction emphasized validated sexual function questionnaires, hormone assays, reward system imaging, and substance use outcomes. Results Randomized controlled trials in healthy men found no significant effect of dulaglutide on sexual desire, testosterone, FSH, LH, or sperm parameters after four weeks. FAERS data identified 182 cases of male sexual dysfunction (orgasmic dysfunction, erectile dysfunction, decreased libido) associated with GLP-1 analogues, but the association was weak and overall patient risk remains low. Narrative reviews highlight inconsistent findings regarding erectile function, with some studies suggesting improvement in metabolic dysfunction settings, but no robust evidence for direct benefit or harm. Gender differences in response to GLP-1 analogues are suggested by preclinical and clinical data, but no clear qualitative differences in sexual function have been established. Adverse effects are primarily gastrointestinal, with rare reports of sexual dysfunction. Importantly, preclinical and translational studies demonstrate that GLP-1 analogues reduce drug intake, attenuate dopamine release in reward circuits, and decrease relapse-like behavior in models of alcohol, nicotine, and psychostimulant addiction. Early human studies suggest potential therapeutic benefit for substance use disorders. These reward-modulating effects may indirectly influence sexual motivation and behavior, particularly in populations with comorbid addiction or reward dysregulation.[ Conclusions In conclusion, current evidence indicates that GLP-1 analogues do not significantly diminish libido or sexual function in healthy adults, However, their ability to modulate central reward pathways and reduce addictive behaviors represents a novel therapeutic avenue, with potential implications for both sexual and addiction medicine. Further research is needed to clarify these interactions in diverse clinical populations. Disclosure No