The Effects of Semaglutide vs Testosterone Replacement Therapy on Functional Hypogonadism and Sperm Quality in Men With Type 2 Diabetes Mellitus and Obesity

NCT ID: NCT06489457

Last Updated: 2024-07-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-20
• Study Completion Date: 2023-06-30

Brief Summary

The goal of this study is to learn whether semaglutide (treatment for type 2 diabetes and obesity) can improve signs and symptoms of hypogonadism in men with type 2 diabetes, obesity and hypogonadism (a condition when levels of testosterone are decreased).

The main questions the study aims to answer are:

• Does semaglutide improve the quality of sperm?
• Does semaglutide improve symptoms of hypogonadism as well as testosterone replacement?

The researchers will compare semaglutide to testosterone replacement to see which drug better treats symptoms of hypogonadism.

• The participants will receive testosterone replacement therapy (intramuscular injection every 10-12 weeks) or magnitude (subcutaneous injection once a week).
• The treatment will last 24 weeks.
• The participants will visit the clinic at the start and the end of the study.

At the visit, the researchers will measure body weight and take a few blood samples. The participants will also be asked to complete several questionnaires and collect a sperm sample.

The participants are free to terminate their participation in the study at any time without giving a reason.

Detailed Description

Men aged 18 - 65 years with type 2 diabetes on oral antidiabetic treatment, body mass index above 30 kg/m2 and functional hypogonadism (total testosterone below 11 nmol/L and at least 2 symptoms of hypogonadism) are eligible to participate in the study. The participants are randomized to either testosterone undecanoate (100 mg intramuscular injection once per 10-12 weeks) or semaglutide (subcutaneous injection once weekly titrated to 1 mg in concordance with Summary of product characteristics (SmPC) for 24 weeks.

At the beginning of the study and after 24 weeks of treatment the researchers measured anthropometric (body weight, body composition), endocrine (total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG)) and metabolic parameters (HbA1c, 75-g oral glucose tolerance test (OGTT), insulin, c-peptide). The participants also gave sperm samples and completed self-reported hypogonadism symptom evaluation (Ageing male symptoms (AMS) score, International Index of erectile function 15 (IIEF-15)).

Conditions

Type 2 Diabetes Mellitus; Obesity; Functional Hypogonadism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Semaglutide Treatment

Group Type: EXPERIMENTAL

Semaglutide

Intervention Type: DRUG

Semaglutide subcutaneous injection once weekly titrated to 1 mg in concordance with Summary of product characteristics (SmPC) (0.25 mg once weekly in the first month, 0.5 mg once weekly in the second month and 1 mg once weekly from the third month onward)

Testosterone Replacement Therapy

Group Type: ACTIVE_COMPARATOR

Testosterone Undecanoate

Intervention Type: DRUG

Testosterone Undecanoate intramuscular injection 1000 mg once per 10-12 weeks

Interventions

Semaglutide

Semaglutide subcutaneous injection once weekly titrated to 1 mg in concordance with Summary of product characteristics (SmPC) (0.25 mg once weekly in the first month, 0.5 mg once weekly in the second month and 1 mg once weekly from the third month onward)

Intervention Type: DRUG

Testosterone Undecanoate

Testosterone Undecanoate intramuscular injection 1000 mg once per 10-12 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• type 2 diabetes mellitus,
• obesity (body mass index (BMI) higher or equal to 30 kg/m^2),
• functional hypogonadism (defined by total testosterone less than 11 nmol/L and 2 or more symptoms of sexual dysfunction)

Exclusion Criteria

• Insulin treatment,
• glucagon-like peptide 1 (GLP-1) agonist treatment,
• sodium-glucose cotransporter-2 (SGLT-2) inhibitor treatment,
• other identified causes of hypogonadism,
• hemochromatosis,
• active malignant disease,
• thrombophilia,
• venous thrombosis within 6 months,
• recent acute myocardial infarction or stroke,
• prostate-specific antigen (PSA) higher than 3 ng/L,
• severe lower urinary tract symptoms with an International Prostate Symptom Score above 19,
• severe sleep apnea syndrome,
• hematocrit higher than 0.5,
• significant kidney or liver disease,
• ongoing treatment with opioid analgesics, antipsychotics, glucocorticoids,
• alcohol abuse,
• severe ongoing mental illness,
• personal history of pancreatitis or medullary thyroid carcinoma,
• personal or family history of multiple endocrine neoplasia type 2.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

University Medical Centre Ljubljana

OTHER

Sponsor Role: lead

Responsible Party

Andrej Janez

Professor, PhD, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University Medical Centre Ljubljana

Ljubljana, , Slovenia

Countries

Slovenia

References

Gregoric N, Sikonja J, Janez A, Jensterle M. Semaglutide improved sperm morphology in obese men with type 2 diabetes mellitus and functional hypogonadism. Diabetes Obes Metab. 2025 Feb;27(2):519-528. doi: 10.1111/dom.16042. Epub 2024 Nov 7.

Reference Type: DERIVED

PMID: 39511836 (View on PubMed)

Other Identifiers

0120-26/2020/13

Identifier Type: OTHER

Identifier Source: secondary_id

SEMA-TESTO Hypogonadism

Identifier Type: -

Identifier Source: org_study_id