Clinical trial NCT06489457: The Effects of Semaglutide vs Testosterone Replacement Therapy on Functional Hypogonadism and Sperm Quality in Men With Type 2 Diabetes Mellitus and Obesity
Official title: The Effects of Semaglutide vs Testosterone Replacement Therapy on Functional Hypogonadism and Sperm Quality in Men With Type 2 Diabetes Mellitus and Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Obesity
Functional Hypogonadism
Keywords: Functional Hypogonadism
Type 2 Diabetes
Obesity
Tesrosterone Replacement Therapy
Semaglutide
GLP-1 agonist
Semen
Sperm
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
First posted: 2024-07-08
Enrollment: 25
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)).

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.

Primary outcomes:
measure: Change in semen volume from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
measure: Change in sperm concentration from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
measure: Change in total motility of sperm from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
measure: Change in normal sperm forms from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
measure: Change in total number of sperm from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
Secondary outcomes:
measure: Change in International index of erectile function 15 (IIEF-15) score from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
measure: Change in Aging male symptoms (AMS) score from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
measure: Change in HbA1c from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
measure: Change in follicle-stimulating hormone (FSH) from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
measure: Change in luteinizing hormone (LH) from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
measure: Change in estimated visceral adipose tissue from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
measure: Change in percentage of body fat from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
measure: Change in fasting serum low-density lipoproteins (LDL) cholesterol from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
measure: Change in fasting serum total cholesterol from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
measure: Change in fasting serum high-density lipoproteins (HDL) cholesterol from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
measure: Change in fasting triglycerides from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
Other outcomes:
measure: Change in body mass from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
measure: Change in body mass index (BMI) from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
measure: Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score from baseline and between the treatment arms
timeFrame: Baseline and 24 weeks
Locations:
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana
Study officials:
References: