Twelve Months of GLP-1 Receptor Agonist Therapy Is Associated with Improved Sperm Quality and Hormonal Profile in Men with Obesity and/or Type 2 Diabetes: A Prospective Cohort Study

Background/Objectives: Obesity and type 2 diabetes mellitus (T2DM) are associated with impaired male reproductive function. We assessed changes in semen quality and reproductive hormones during 12 months of glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy. Methods: In this prospective, single-center cohort study, 161 men with obesity and/or T2DM initiated semaglutide or liraglutide. Semen parameters, reproductive hormones, and metabolic indices were assessed at baseline and 12 months. Paired comparisons were performed in 108 completers (54 receiving each agent), with Holm adjustment for five principal semen endpoints. Total progressive motile sperm count (TPMSC) was evaluated post hoc. Baseline characteristics of completers and non-completers were compared. Results: Body mass index decreased from 37.5 to 31.3 kg/m2 and HbA1c from 6.49% to 5.64%. Sperm concentration increased from 62.9 to 86.7 × 106/mL, progressive motility from 22.8% to 38.4%, and normal morphology from 3.14% to 4.46% (all p < 0.001). Total sperm number increased but did not remain statistically significant after Holm correction (adjusted p = 0.062). Exploratory TPMSC increased from 42.4 to 80.9 × 106/ejaculate (p < 0.001). Total testosterone increased from 5.91 to 7.74 nmol/L, whereas estradiol decreased from 36.5 to 28.4 pg/mL (both p < 0.001). Fifty-three participants (32.9%) did not complete follow-up; non-completers were older and more frequently had T2DM. Conclusions: Twelve months of GLP-1 RA therapy coincided with improved semen laboratory parameters, higher total testosterone, and improved metabolic status. The uncontrolled design and selective attrition preclude causal inference or conclusions about fertility outcomes.