The Effect of Weekly Semaglutide Treatment on Energy Expenditure

NCT ID: NCT06390501

Last Updated: 2026-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-01
• Study Completion Date: 2025-09-15

Brief Summary

This study will test the effects of weekly injections of the glucagon like peptide-1 (GLP-1) agonist semaglutide on energy expenditure and metabolic parameters in a 24 week double-blind, placebo-controlled dose escalation randomized trial. After baseline testing, 52 patients will be randomly assigned to the semaglutide or matching placebo injection group. In addition to taking medication or placebo, all participants will a calorie restricted diet provided by the researchers, providing 600 kcals per day below their estimated baseline requirements. Before and at the end of treatment, weight status, body composition, basal metabolic rate (BEE), 24h energy expenditure, daily total energy expenditure (TEE) for free living, physical activity, energy intake (questionnaire and food table), and hormone parameters for energy homeostasis will be evaluated.

Detailed Description

Obesity is a complex chronic recurrent multifactorial disease characterized by abnormal or excessive body fat, which impairs physical health. In recent years, the glucagon like peptide-1 (GLP-1) receptor agonist semaglutide has attracted much attention due to its significant impact on weight loss. It can not only effectively control blood sugar by regulating the secretion of insulin and glucagon. It can also participate in certain brain regions of the body at pharmacological doses, regulating food intake and consumption. Semaglutide reduces energy intake and achieves weight loss by delaying gastric emptying, suppressing appetite, reducing hunger, and increasing satiety. This effect has been proven to be produced by activating the glucagon like peptide-1 (GLP-1) receptors in the central nervous system, further indirectly regulating the activity of neurons involved in appetite regulation, food intake, and preference.

The previous results of using GLP-1 receptor agonist (RA) in rats and humans provide promising evidence data to support current randomized clinical trials. Peripheral administration of GLP-1 or GLP-1 RA can reduce blood sugar and energy intake in humans and rodents, and long-term treatment can lead to weight loss. In mice the drug also sustains energy expenditure at levels similar to controls, preventing the reduction that normally accompanies caloric restriction. Whether the same effects occur in humans is unclear because no studies have yet been performed comparing semaglutide treated individuals with those on a standard calorie restricted diet (in effect pair feeding). Therefore, in this study, researchers will use doubly- labelled water (DLW) and respiratory chambers to investigate whether semaglutide can prevent the reduction of energy expenditure that typically occurs during energy restriction.

Conditions

Obesity; Drug

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Semaglutide

Once-weekly injections of gradually increased doses of semaglutide

Group Type: EXPERIMENTAL

Semaglutide

Intervention Type: DRUG

Solution for subcutaneous (s.c. - under the skin) injection. 0.25 mg semaglutide once weekly for four weeks, 0.5 mg semaglutide once weekly for four weeks, 0.1 mg semaglutide once weekly for four weeks, 1.7 mg semaglutide once weekly for four weeks followed by 2.4 mg semaglutide once weekly for eight weeks

Placebo

Once-weekly injections of gradually increased volumes of saline placebo, to match the volumes of the semaglutide treated arm.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Solution for subcutaneous (s.c. - under the skin) injection

Interventions

Semaglutide

Solution for subcutaneous (s.c. - under the skin) injection. 0.25 mg semaglutide once weekly for four weeks, 0.5 mg semaglutide once weekly for four weeks, 0.1 mg semaglutide once weekly for four weeks, 1.7 mg semaglutide once weekly for four weeks followed by 2.4 mg semaglutide once weekly for eight weeks

Intervention Type: DRUG

Placebo

Solution for subcutaneous (s.c. - under the skin) injection

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age 18-60 years at time of enrollment

2. BMI ≥ 25 kg/m²

Exclusion Criteria

1. Weight change exceeding 5 kilograms (11 pounds) in the past 90 days

2. Surgical treatment for past obesity, dieting, or undergoing weight loss treatment

3. Irregular diet and lifestyle, unhealthy habits such as smoking, alcohol, and drugs

4. Patients with metabolic diseases, basic diseases or infectious diseases

5. Patients with a personal or family history of medullary thyroid carcinoma (MTC), or patients with rare type 2 multiple endocrine tumor syndrome (MEN 2)

6. Current use of any other GLP1 receptor agonist

7. Pregnancy, lactation or expectation to conceive during study period (8) Subject with contraindication to neuroimaging by MRI (9) People with fear of blood and pathologically low blood pressure (10) Use of antibiotics and probiotics within 8 weeks

11) Subject unlikely to adhere to study procedures in opinion of investigator

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Shenzhen Institutes of Advanced Technology ,Chinese Academy of Sciences

OTHER

Sponsor Role: lead

Responsible Party

John R. Speakman

Professor, Chief Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

John R Speakman

Role: STUDY_CHAIR

Shenzhen Institutes of Advanced Technology ,Chinese Academy of Sciences

Locations

Shenzhen Institute of Advanced Technology

Shenzhen, , China

Countries

China

Other Identifiers

SIAT-IRB-231215-H0705

Identifier Type: -

Identifier Source: org_study_id