MON-708 Effect of Incretin-Based Weight Loss Drugs on Testosterone Concentrations in Men

Abstract Disclosure: S. Portillo Canales: None. I. Iqbal: None. R. Akande: None. E. Wood: None. S.G. Albert: None. S. Dhindsa: None. Background: Obesity and type 2 diabetes in men are associated with reduced serum total and free testosterone (T). Weight loss from bariatric surgery or lifestyle interventions increases total and free T. Incretin therapies based on glucagon-like peptide-1 or gastric inhibitory peptide receptor agonism are now commonly used for weight loss in obesity or diabetes. We evaluated the effect of incretin therapies on testosterone concentrations in men.Methods: This retrospective cohort study used electronic health records. Chart reviews were conducted for adult men who had 1) at least one health system interaction from July-December 2024, 2) received incretin treatment, 3) were not treated with T, clomiphene, hCG, aromatase inhibitors, or androgen supplements, 4) had total T measured more than once, with at least one measurement during incretin treatment (intention to treat analysis). 110 men qualified. As weight loss increases sex hormone binding globulin (SHBG), free T measurement is essential in obese men to assess gonadal status. Two or more free T concentrations were available in 54 men. Averages are mean ± SD. Paired t-tests compared groups, and Pearson correlation evaluated variables of interest.Results: Mean age was 54±11 years; 80% were white, 10% black. Semaglutide, dulaglutide, and tirzepatide were used by 68%, 16%, and 38%, while 27% used more than one therapy. Type 2 diabetes was present in 86 men; 86% were on oral hypoglycemics, 21% used insulin. Incretin therapy duration was 1.6±1.0 years. Baseline T measurements were 0.8±1.5 years pre-incretins. Mean body weight and BMI at baseline were 116±27 kg and 35±7 kg/m². Final body weight was 104±30 kg (p<0.001). Total T and free T increased from 322±111 and 7.0±3.0 ng/dL to 380±130 and 8.2±3.8 ng/dL (p<0.001 and 0.004). SHBG was 36±17 nmol/L at baseline and 38±17 nmol/L at final T (p=0.23). HbA1c at baseline and end were 7.2±1.7 and 6.5±1.3% (p=0.001). Weight change correlated negatively with total T (r=-0.30, p=0.002) and free T (r=-0.28, p=0.04), and trended with SHBG (r=-0.30, p=0.06). Patients with normal total T (>300 ng/dL) increased from 53% to 77% (p<0.001). Conclusion: Incretin therapy increases total and free T in men, likely due to weight loss. A 10% weight loss significantly increased the proportion of men with normal testosterone. Presentation: Monday, July 14, 2025