Effect of Semaglutide on Sperm Concentration in Overweight Infertile Men: A Randomized Placebo‑Controlled Trial

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What is this study about?

The study focuses on men who have difficulty conceiving (Infertility) and who are also classified as overweight. The medication being tested is a weekly injection called semaglutide, delivered with a pre‑filled pen that places the dose under the skin (subcutaneous). A matching pen that contains no active drug (placebo) is used for comparison.

The purpose is to determine whether the medication changes the number of sperm produced, measured as sperm concentration, compared with the placebo. Participants receive an injection once a week for several months and attend a few clinic visits where blood samples, body measurements and semen samples are collected to evaluate sperm count, hormone levels and other health markers. No surgery is involved, and the follow‑up period lasts about six months.

1 baseline visit and randomization

on the first day in the study you attend a baseline visit where a sperm sample, blood tests, weight, body mass index (bmi), and body composition scan (dxa) are performed. questionnaires about symptoms of androgen deficiency and sexual function are also completed.

after the assessments you are randomly assigned to receive either semaglutide 2.4 mg or a placebo. you are given a pre‑filled pen and instructions on how to give a subcutaneous injection (injection under the skin).

2 start weekly injections

starting on the day of randomization you inject 2.4 mg of the assigned product once a week using the pen. the injection is given under the skin of the abdomen or thigh.

you continue the weekly injections for the entire study period, which lasts until day 300 (about ten months). the schedule is the same for both the active drug and the placebo.

3 first follow‑up visit (day 100)

approximately three months after the first injection you return for a follow‑up visit. a new sperm sample is collected and analyzed for concentration and total count.

blood tests are repeated to measure testosterone, luteinizing hormone (lh), follicle‑stimulating hormone (fsh), and other hormones. weight, bmi, and questionnaires are updated.

the study staff checks your injection technique, reviews any side effects, and confirms that you are continuing the weekly injections.

4 second follow‑up visit (day 200)

around six months after starting treatment you attend the second follow‑up. the primary outcome of the study – sperm concentration and total sperm count – is measured again.

additional blood tests assess hormone levels, cholesterol, hbA1c, and insulin resistance (homa‑ir). weight, bmi, and questionnaires are repeated.

the weekly injection schedule remains unchanged.

5 final follow‑up visit (day 300)

at about ten months you complete the final visit. a comprehensive sperm analysis is performed, including dna fragmentation index and evaluation of motility, morphology, and total motile sperm.

a dxa scan evaluates body composition, total body fat, muscle mass, bone mineral density (bmd), and trabecular bone score (tbs).

blood tests again measure testosterone, lh, fsh, sex hormone‑binding globulin (shbg), estradiol, amh, inhibin b, cholesterol fractions, hbA1c, and homa‑ir.

questionnaires on androgen deficiency and sexual function are completed for the last time.

6 study completion

after the day 300 visit the study drug is stopped. you return any remaining pens and receive information about the study results when they become available.

no further study‑specific visits are required unless a separate follow‑up is arranged by your health care provider.

Who Can Join the Study?

You must sign a written agreement called informed consent that shows you understand the study before any study procedures are done; this document explains the study and records your permission to take part.
You must be a man who is between 18 and 60 years old when you sign the consent form.
You must have infertility and at least one of the following sperm test results:
- Sperm concentration (the number of sperm in each milliliter of semen) less than 16 million.
- Less than 42% of sperm that can move, called motile spermatozoa.
- Less than 4% of sperm that look normal in shape, called morphologically normal spermatozoa.
Your body mass index, known as BMI, must be 27 or higher; BMI is a calculation using your height and weight to show if you are overweight.

Who Cannot Join the Study?

Having Type 1 diabetes, a condition where the body cannot produce insulin.
Being overweight because of hormone problems such as Cushing’s syndrome, which causes excess cortisol.
Taking any prescription or over‑the‑counter medicine (other than routine vitamins, occasional paracetamol, aspirin, or ibuprofen) that could affect how the study drug is absorbed, moves, or works in the body (pharmacokinetic or pharmacodynamic effects).
Having a past history of pancreatitis, which is inflammation of the pancreas.
Using morphine every day, a strong pain medication.
Having surgery planned during the study period, except for very small procedures that do not involve the stomach or intestines.
Having previously undergone bariatric surgery, a type of weight‑loss surgery.
Having any current or past cancer (except common skin cancers called basal cell skin cancer or squamous cell skin cancer) that could affect the study results.
Being unable or unwilling to give yourself an injection during the screening visit with a test pen (self‑injection).
Having mental or language difficulties, or being unwilling to follow the study rules, that would prevent proper understanding or cooperation (mental incapacity or language barriers).
Having poorly controlled type 2 diabetes as judged by the doctor.
Having a total sperm count higher than 80 million per milliliter (total sperm count >80 mio/mL).
Having a low blood level of the hormone FSH (less than 2 IU/L).
Having a very low sperm concentration (less than 1 million per milliliter, sperm concentration < 1 mio/mL).
Having a body‑mass index (BMI) greater than 50 kg/m², indicating severe obesity.
Having reduced kidney function with an estimated glomerular filtration rate (GFR) below 45 ml/min/1.73 m².
Having known chromosome problems (chromosomal aberrations) except for small deletions on the Y chromosome.
Having a detected mutation in the CFTR gene, which is linked to cystic fibrosis.
Having used a GLP‑1RA (a diabetes medication that activates the GLP‑1 receptor) within the past 6 months.
Having any other health condition that the doctor believes could make participation unsafe or difficult to follow.

Where you can join this trial?

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Other Sites

Site Name	City	Country	Status
Hxxqyv Hzglaawr	Herlev	Denmark

Trial status

Country	Status	Recruitment Start
Denmark	Not yet recruiting	01.01.2027

Trial locations

Investigated Drugs:

Semaglutide

Semaglutide is a medication given as an injection under the skin once a week. It works like a natural hormone that helps control blood sugar and can also reduce appetite, leading to weight loss. In this trial, the drug is being studied to see if it can improve sperm concentration in overweight men who have difficulty conceiving.

Investigated Diseases:

Infertility – Infertility is the inability to achieve a pregnancy after at least one year of regular, unprotected sexual intercourse. In men, it commonly reflects reduced sperm production, poor sperm quality, or problems with sperm delivery. The condition may develop gradually as hormonal or genetic factors, health issues, or lifestyle influences affect testicular function. As the underlying cause persists, sperm count and other parameters can continue to decline over time.

Overweight – Overweight describes a body weight that exceeds the healthy range for a given height, typically defined by a body‑mass index of 25–29.9 kg/m². It usually results from a gradual surplus of calories over energy expenditure, leading to increased fat stores. Over time, excess weight can accumulate further and affect metabolism and organ function. If lifestyle patterns remain unchanged, the amount of body fat may continue to rise.

Trial ID:

2026-527538-29-00

Trial Phase:

Therapeutic exploratory (Phase II)

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Effect of Semaglutide on Sperm Concentration in Overweight Infertile Men: A Randomized Placebo‑Controlled Trial

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?