Semaglutide improved sperm morphology in obese men with type 2 diabetes mellitus and functional hypogonadism.

Gregorič, Nadan; Šikonja, Jaka; Janež, Andrej; Jensterle, Mojca

Aims: To compare the effects of semaglutide and testosterone replacement therapy (TRT) on semen quality and parameters of functional hypogonadism (FH) in men with type 2 diabetes mellitus and obesity. Materials and Methods: We designed a randomised open‐label trial in 25 men with type 2 diabetes (aged 50 [46–60] years, BMI 35.9 [32.8–38.7] kg/m2) and FH randomised to semaglutide (SEMA) 1 mg/week or intramuscular testosterone undecanoate (TRT) 1000 mg/10–12 weeks for 24 weeks. Semen analysis and parameters of FH were measured at baseline and after 24 weeks of treatment. Participants completed questionnaires of the International Index of Erectile Function‐15 (IIEF‐15) and the Aging Symptoms in Men (AMS). Results: The quality of baseline sperm parameters of our study cohort was poor, below the 5th percentile of reference values. In the SEMA group, there was a significant increase in morphologically normal sperm from baseline to the end of the study (2% [2; 3.5] vs. 4% [2; 5.5]; p = 0.012), whereas sperm concentration and total number decreased significantly in the TRT group. Compared to TRT, the SEMA group had a significantly higher number of morphologically normal sperm, sperm concentration and total number. Both groups experienced an increase in total testosterone and improvement in the AMS score, whereas the IIEF‐15 score significantly improved only in the TRT group. Conclusion: Semaglutide markedly improved sperm morphology, total testosterone levels and symptoms of hypogonadism. These findings highlight semaglutide's potential as a therapeutic approach for men with obesity‐related FH who desire fertility. Clinical trial registration number: NCT06489457, www.clinicaltrials.gov.

TYPE 2 diabetes; SEMEN analysis; OLDER men; SEMAGLUTIDE; OVERWEIGHT men

Diabetes, Obesity & Metabolism, 2025, Vol 27, Issue 2, p519

1462-8902

Academic Journal

10.1111/dom.16042