Neutral effect of exenatide on serum testosterone in men with type 2 diabetes mellitus: A prospective cohort

Background: Endogenous testosterone increases with weight loss from diet, exercise, and bariatric surgery. However, little is known about testosterone levels after weight loss from medication. Objectives: Uncover the effects of Glucagon-Like Peptide-1 receptor agonist (GLP-1 RA) therapy on serum testosterone. Material and Methods: Prospective cohort study of men starting GLP-1 RA therapy for type 2 diabetes mellitus. Results: 51 men lost 2.27 kg (p = 0.00162) and their HbA1c values improved by 0.7% (p = 0.000503) after 6 months of GLP-1 RA therapy. There was no significant change in testosterone for the group as a whole. However, in subgroup analyses, there was a significant difference in total testosterone change between men starting with baseline total testosterone <320 ng/dL (238.5 ± 56.5 ng/dL to 272.2 ± 82.3 ng/dL) compared to higher values (438 ± 98.2 ng/dL to 412 ± 141.2 ng/dL) (p = 0.0172);free testosterone increased if the baseline total testosterone was <320 ng/dL (55.2 ± 12.8 pg/mL to 57.2 ± 17.6 pg/mL) and decreased if >320 ng/dL (74.7 ± 16.3 pg/mL to 64.2 ± 17.7 pg/mL) (p = 0.00807). Additionally, there were significant differences in testosterone change between men with HbA1c improvements ≥1% (351.6 ± 123.9 ng/dL to 394.4 ± 136.5 ng/dL) compared to men with HbA1c changes <1% (331.8 ± 128.6 ng/dL to 316.1 ± 126.2 ng/dL) (p = 0.0413). Conclusion: GLP-1 RA therapy improves weight and HbA1c without adverse effects on testosterone. Those starting with lower testosterone values or attaining greater improvement in HbA1c may see additional benefits.