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

NCT06489457 | Completed Phase 3

• 2 other identifiers: SEMA-TESTO Hypogonadism0120-26/2020/13
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes Mellitus; Obesity; Functional Hypogonadism

Keywords

Functional Hypogonadism; Type 2 Diabetes; Obesity; Tesrosterone Replacement Therapy; Semaglutide; GLP-1 agonist; Semen; Sperm

Outcome Measures

Primary Outcomes (5)

• Change in semen volume from baseline and between the treatment arms

  The semen volume will be measured and reported in mililiters (mL). The higher the value the better the outcome.

  Baseline and 24 weeks

• Change in sperm concentration from baseline and between the treatment arms

  The sperm concentration will be measured and reported in number times 10\^6 per mililiter (10\^6/mL). The higher the value the better the outcome.

  Baseline and 24 weeks

• Change in total motility of sperm from baseline and between the treatment arms

  The total motility will be assessed as total number of motile sperm and reported as number times 10\^6 per ejaculate (10\^6/ejaculate). The higher the value the better the outcome.

  Baseline and 24 weeks

• Change in normal sperm forms from baseline and between the treatment arms

  The normal sperm forms will be assessed as total number of sperm with normal morphology and reported as number times 10\^6 per ejaculate (10\^6/ejaculate). The higher the value the better the outcome.

  Baseline and 24 weeks

• Change in total number of sperm from baseline and between the treatment arms

  The total number of sperm will be measured and reported in number times 10\^6 per ejaculate (10\^6/ejaculate). The higher the value the better the outcome.

  Baseline and 24 weeks

Secondary Outcomes (11)

• Change in International index of erectile function 15 (IIEF-15) score from baseline and between the treatment arms

  Baseline and 24 weeks

• Change in Aging male symptoms (AMS) score from baseline and between the treatment arms

  Baseline and 24 weeks

• Change in HbA1c from baseline and between the treatment arms

  Baseline and 24 weeks

• Change in follicle-stimulating hormone (FSH) from baseline and between the treatment arms

  Baseline and 24 weeks

• Change in luteinizing hormone (LH) from baseline and between the treatment arms

  Baseline and 24 weeks

Other Outcomes (3)

• Change in body mass from baseline and between the treatment arms

  Baseline and 24 weeks

• Change in body mass index (BMI) from baseline and between the treatment arms

  Baseline and 24 weeks

• Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score from baseline and between the treatment arms

  Baseline and 24 weeks

Study Arms (2)

Semaglutide Treatment

EXPERIMENTAL

Drug: Semaglutide

Testosterone Replacement Therapy

ACTIVE COMPARATOR

Drug: Testosterone Undecanoate

Interventions

Semaglutide 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)

Semaglutide Treatment

Testosterone Undecanoate DRUG

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

Testosterone Replacement Therapy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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,

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead

Study Sites (1)

University Medical Centre Ljubljana

Ljubljana, 1000, Slovenia

Location

Related Publications (1)

• 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.

  PMID: 39511836 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity

Interventions

semaglutide; testosterone undecanoate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, PhD, MD

Study Record Dates

• First Submitted: June 18, 2024
• First Posted: July 8, 2024
• Study Start: September 20, 2020
• Primary Completion: May 11, 2023
• Study Completion: June 30, 2023
• Last Updated: July 8, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1)