Type 2 Diabetes MellitusPhase 3SEMATNCT06489457
The Effects of Semaglutide vs Testosterone Replacement Therapy on Functional Hypogonadism and Sperm Quality in Men With Type 2 Diabetes Mellitus and Obesity
A Phase 3 study testing Semaglutide and Testosterone Undecanoate in people with Type 2 Diabetes Mellitus and Obesity, run by University Medical Centre Ljubljana at 1 site in Slovenia.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years, men only
- Conditions the study is for
- Type 2 Diabetes Mellitus, Obesity, Functional Hypogonadism
- What is being tested?
- Semaglutide and Testosterone Undecanoate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteSlovenia
- Study dates
- 20 Sep 2020to 30 Jun 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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,
Show all 19Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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:
Read more
- 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.
Read the 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
- Being tested
- Semaglutide, Testosterone Undecanoate
- Keywords
- Functional Hypogonadism, Type 2 Diabetes, Obesity, Tesrosterone Replacement Therapy, Semaglutide, GLP-1 agonist, Semen, Sperm
- Medical subject headings
- Diabetes Mellitus, Type 2, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SemaglutideDrug
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 UndecanoateDrug
Testosterone Undecanoate intramuscular injection 1000 mg once per 10-12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Semaglutide Treatment | Experimental | Not described Receives: Drug: Semaglutide |
| Testosterone Replacement Therapy | Active comparator | Not described Receives: Drug: Testosterone Undecanoate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
IIEF-15 assesses male sexual function. It has 5 domains. Erectile function with scoring range from 30 (max) to 1 (min). Orgasmic function with scoring range from 10 (max) to 1 (min). Sexual desire with scoring range from 10 (max) to 2 (min). Intercourse satisfaction with scoring range from 15 (max) to 0 (min). Overall satisfaction with scoring range from 10 (max) to 2 (min). The subdomains combine to overall score with scoring range from 75 (max) to 6 (min). The higher score indicates the better sexual function.
Measured: Baseline and 24 weeks
Change in Aging male symptoms (AMS) score from baseline and between the treatment arms
The AMS score assesses male symptoms os hypogonadism. It has 3 subdomains. Psychological symptoms with scoring range from 25 (max) to 5 (min). Somatic with scoring range from 35 (max) to 7 (min). Sexual with scoring range from 25 (max) to 5 (min). The subdomains combine to overall score with scoring range from 85 (max) to 17 (min). The lower the score the less symptoms are present.
Measured: Baseline and 24 weeks
Change in HbA1c from baseline and between the treatment arms
The HbA1c will be measured and reported in % and milimoles per mole (mmol/mol). The lower the value the better the outcome.
Measured: Baseline and 24 weeks
Change in follicle-stimulating hormone (FSH) from baseline and between the treatment arms
The FSH will be measured and reported in international units per liter (IU/L). The higher the value the better the outcome.
Measured: Baseline and 24 weeks
Change in luteinizing hormone (LH) from baseline and between the treatment arms
The LH will be measured and reported in international units per liter (IU/L). The higher the value the better the outcome.
Measured: Baseline and 24 weeks
Change in estimated visceral adipose tissue from baseline and between the treatment arms
Measured by dual-energy X-ray absorptiometry the estimated visceral adipose tissue will be reported in grams (g). The lower the value the better the outcome.
Measured: Baseline and 24 weeks
Change in percentage of body fat from baseline and between the treatment arms
Measured by dual-energy X-ray absorptiometry the procentage of body fat will be reported in %. The lower the value the better the outcome.
Measured: Baseline and 24 weeks
Change in fasting serum low-density lipoproteins (LDL) cholesterol from baseline and between the treatment arms
The LDL cholesterol will be measured and reported in milimoles per liter (mmol/L). The lower the value the better the outcome.
Measured: Baseline and 24 weeks
Change in fasting serum total cholesterol from baseline and between the treatment arms
The total cholesterol will be measured and reported in milimoles per liter (mmol/L). The lower the value the better the outcome.
Measured: Baseline and 24 weeks
Change in fasting serum high-density lipoproteins (HDL) cholesterol from baseline and between the treatment arms
The HDL cholesterol will be measured and reported in milimoles per liter (mmol/L). The higher the value the better the outcome.
Measured: Baseline and 24 weeks
Change in fasting triglycerides from baseline and between the treatment arms
Triglycerides will be measured and reported in milimoles per liter (mmol/L). The lower the value the better the outcome.
Measured: Baseline and 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2024
- Study start20 Sep 2020
- Primary completion11 May 2023
- Study completion30 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by University Medical Centre LjubljanaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Ljubljana
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrej Janez, University Medical Centre Ljubljana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06489457
- Sponsor's protocol ID
- SEMA-TESTO Hypogonadism
- Other IDs
- 0120-26/2020/13
- Acronym
- SEMAT
- Status last verified
- Jul 2024
- First submitted
- 18 Jun 2024
- Last updated
- 8 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We have not decided how and when IPD and the supporting information will be shared. The documents also need to be translated into English. It might take some time.
Publications
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.
PubMed 39511836
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06489457
- Acronym / sponsor ID
- SEMAT / SEMA-TESTO Hypogonadism
- Conditions
- Type 2 Diabetes Mellitus, Obesity, Functional Hypogonadism
- Keywords
- Functional Hypogonadism, Type 2 Diabetes, Obesity, Tesrosterone Replacement Therapy, Semaglutide, GLP-1 agonist, Semen, Sperm
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University Medical Centre LjubljanaUniversity, hospital or other
- Study start
- 20 Sep 2020 (actual)
- Primary completion
- 11 May 2023 (actual)
- Study completion
- 30 Jun 2023 (actual)
- First posted
- 8 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Semaglutide Treatment | Experimental | Drug: Semaglutide |
| Testosterone Replacement Therapy | Active comparator | Drug: Testosterone Undecanoate |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (19 listed)
- Insulin treatment,
- glucagon-like peptide 1 (GLP-1) agonist treatment,
- sodium-glucose cotransporter-2 (SGLT-2) inhibitor treatment,
- other identified causes of hypogonadism,
- hemochromatosis,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SemaglutideSemaglutide 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) | Drug | Semaglutide Treatment |
| Testosterone UndecanoateTestosterone Undecanoate intramuscular injection 1000 mg once per 10-12 weeks | Drug | Testosterone Replacement Therapy |
Primary outcome
Change in semen volume from baseline and between the treatment arms
Time frame: Baseline and 24 weeks
The semen volume will be measured and reported in mililiters (mL). The higher the value the better the outcome.
Change in sperm concentration from baseline and between the treatment arms
Time frame: Baseline and 24 weeks
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.
Change in total motility of sperm from baseline and between the treatment arms
Time frame: Baseline and 24 weeks
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.
Change in normal sperm forms from baseline and between the treatment arms
Time frame: Baseline and 24 weeks
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.
Change in total number of sperm from baseline and between the treatment arms
Time frame: Baseline and 24 weeks
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.
11 secondary outcomes
Change in International index of erectile function 15 (IIEF-15) score from baseline and between the treatment arms
Time frame: Baseline and 24 weeks
Change in Aging male symptoms (AMS) score from baseline and between the treatment arms
Time frame: Baseline and 24 weeks
Change in HbA1c from baseline and between the treatment arms
Time frame: Baseline and 24 weeks
Change in follicle-stimulating hormone (FSH) from baseline and between the treatment arms
Time frame: Baseline and 24 weeks
Change in luteinizing hormone (LH) from baseline and between the treatment arms
Time frame: Baseline and 24 weeks
Change in estimated visceral adipose tissue from baseline and between the treatment arms
Time frame: Baseline and 24 weeks
Change in percentage of body fat from baseline and between the treatment arms
Time frame: Baseline and 24 weeks
Change in fasting serum low-density lipoproteins (LDL) cholesterol from baseline and between the treatment arms
Time frame: Baseline and 24 weeks
Change in fasting serum total cholesterol from baseline and between the treatment arms
Time frame: Baseline and 24 weeks
Change in fasting serum high-density lipoproteins (HDL) cholesterol from baseline and between the treatment arms
Time frame: Baseline and 24 weeks
Change in fasting triglycerides from baseline and between the treatment arms
Time frame: Baseline and 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2024.
- Derived from this study: PubMed 39511836Gregoric 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.
- Individual participant dataSharing planned: No. We have not decided how and when IPD and the supporting information will be shared. The documents also need to be translated into English. It might take some time.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Semaglutide and Testosterone Undecanoate in people with Type 2 Diabetes Mellitus and Obesity, run by University Medical Centre Ljubljana at 1 site in Slovenia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in semen volume from baseline and between the treatment arms (time frame: Baseline and 24 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06489457, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2024.