Semaglutide and Granisetron for Tolerability in Overweight Adults Without Diabetes

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What is this study about?

This clinical trial is being done in adults with overweight and obesity who do not have diabetes. The study looks at semaglutide, a medicine given as a subcutaneous injection under the skin, and compares it with a placebo. Some people also receive granisetron, a medicine taken by mouth. The purpose of the study is to see whether the extra medicine can help people tolerate semaglutide better.

The study follows a short treatment period after semaglutide is given. During this time, the study team checks how well the medicine is tolerated and records common stomach and body symptoms such as nausea, vomiting, constipation, diarrhoea, abdominal pain, dizziness, fatigue, headache, appetite changes, and changes in body weight. The main focus is on how strong nausea is during the first few days after treatment.

The trial is randomised, which means the study treatment is assigned by chance, and double-blind, which means neither the participants nor the study team know who receives which treatment during the study. The trial is also placebo-controlled, so one group receives placebo instead of the active added medicine.

1 study treatment begins

After joining the study, you receive semaglutide as a 0.75 mg subcutaneous injection. A subcutaneous injection is given under the skin.

You also start taking granisetron by mouth at a dose of 2 mg. This oral medicine is the background treatment, meaning it is given alongside the study treatment.

The study also includes a placebo made of rice flour. A placebo is a substance without active medicine.

2 first 96 hours after semaglutide

During the first 96 hours after you receive semaglutide, your nausea is measured using a 0 to 10 numeric rating scale. On this scale, 0 means no nausea and 10 means the worst possible nausea.

Your tolerability of the treatment is assessed during this period by looking at the severity of nausea.

3 daily follow-up during treatment

You report your daily well-being using a numerical rating scale.

You record whether you use the daily oral study medication.

Your appetite is checked for changes.

Your body weight is measured for change from the starting point.

Any side effects are noted, including vomiting, constipation, diarrhoea, abdominal pain, dizziness, fatigue, and headache.

Who Can Join the Study?

Be an adult between 18 and 70 years old.
Have overweight based on body mass index, also called BMI, which is a measure of body weight compared with height:
- BMI 30 to 35 kg/m², or
- BMI 27 to 30 kg/m² and at least one health problem related to excess weight, such as:
  - High blood pressure (hypertension)
  - A history of heart or blood vessel disease, such as heart attack (myocardial infarction), stroke, or heart failure
  - Metabolic dysfunction-associated steatotic liver disease, which means fat buildup in the liver
  - Osteoarthritis, which is joint wear and pain
  - Sleep apnoea, which means repeated pauses in breathing during sleep
Have not used semaglutide, another GLP-1 receptor agonist (a medicine that acts like a gut hormone), or acamprosate during the last 3 months.
Have not used antiemetics (medicines that prevent nausea and vomiting), laxatives (medicines that help bowel movements), or gastrointestinal modulators (medicines that change how the stomach and intestines work) during the last 2 months.
Be not currently taking any medicine that affects stomach or bowel function.
Have no diabetes and no other serious long-term illness.
If a woman can become pregnant, agree to use effective birth control during the whole study. Acceptable methods include:
- Hormonal contraception, such as the pill, patch, injection, or implant
- Intrauterine device (IUD), a small device placed in the uterus
- Intrauterine hormone-releasing system, a device placed in the uterus that releases hormone
- Bilateral tubal occlusion, meaning both fallopian tubes have been blocked or closed
- A partner who has had a vasectomy, meaning a procedure that prevents sperm from being released
- Condom, diaphragm, or cervical cap
- Sexual abstinence, meaning no sexual activity
Be willing to follow all study procedures.
Be able to understand the study and give informed consent, meaning they agree to take part after receiving and understanding the study information.

Who Cannot Join the Study?

FSH below 25.8 U/L in women who have had no menstrual periods for at least 1 year. FSH means follicle-stimulating hormone, a hormone measured in the blood.
A positive urine pregnancy test in women who have had menstrual periods within the last year.
Kidney function that is not good enough for treatment as an outpatient, shown by eGFR of 45 mL/min/1.73 m² or lower. eGFR is a test that estimates how well the kidneys filter the blood.
Liver blood tests that are too high: ASAT or ALAT at least 3 times the upper normal limit, which means 150 U/L or more for men and 105 U/L or more for women. These are liver enzymes, which are proteins that can rise when the liver is irritated or damaged.
Bilirubin at least 1.5 times the upper normal limit, which means 31.5 µmol/L or more. Bilirubin is a substance made when the body breaks down old red blood cells, and a high level can suggest liver or bile duct problems.
A known allergy or sensitivity to semaglutide or any of its ingredients.
Currently breastfeeding.

Where you can join this trial?

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Verified Sites

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Other Sites

Site Name	City	Country	Status
Tartu University Hospital	Tartu	Estonia

Trial status

Country	Status	Recruitment Start
Estonia	Not yet recruiting	01.05.2026

Trial locations

Investigated drugs:

Semaglutide is the main study medicine. It is given as a shot under the skin and is being tested to help people with overweight who do not have diabetes. In this trial, researchers are looking at whether it is easier to tolerate when used with an extra supportive treatment.

Granisetron is a supportive medicine taken by mouth. It is used to help prevent or reduce nausea and vomiting, which can be side effects of semaglutide. In this study, it is being given to see if it improves how well people can stay on semaglutide.

Investigated diseases:

Overweight and obesity – Overweight and obesity are conditions in which a person has more body fat than is considered healthy for their height. They usually develop gradually when energy intake is higher than energy use over time, leading to increasing body weight. The condition may begin as mild excess weight and progress to more marked obesity if weight gain continues. It can remain stable, improve, or worsen depending on long-term changes in body weight and lifestyle.

Trial ID:

2025-524612-11-00

Protocol code:

SEMTOL 1.0

Trial Phase:

Therapeutic confirmatory (Phase III)

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Semaglutide and Granisetron for Tolerability in Overweight Adults Without Diabetes

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?