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Completed

NCT Number: NCT06390501

The Effect of Weekly Semaglutide Treatment on Energy Expenditure

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.

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Key information

Conditions

Obesity; Drug Body Weight Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–60 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Shenzhen Institute of Advanced Technology

Shenzhen, China

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18-60 years at time of enrollment
  • BMI ≥ 25 kg/m²

Exclusion criteria

  • Weight change exceeding 5 kilograms (11 pounds) in the past 90 days
  • Surgical treatment for past obesity, dieting, or undergoing weight loss treatment
  • Irregular diet and lifestyle, unhealthy habits such as smoking, alcohol, and drugs
  • Patients with metabolic diseases, basic diseases or infectious diseases
  • Patients with a personal or family history of medullary thyroid carcinoma (MTC), or patients with rare type 2 multiple endocrine tumor syndrome (MEN 2)
  • Current use of any other GLP1 receptor agonist
  • 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
  • Subject unlikely to adhere to study procedures in opinion of investigator

Treatment and study plan

semaglutide

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

Drug

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

Primary outcomes

  1. Changes of Total Energy Expenditure Assessed by Doubly Labeled Water Analysis

    Time frame: From baseline at week 0 to week 24

    TEE will be measured using the DLW method. Urine samples from all participants in the DLW subset will be stored at -20 ℃ and shipped on dry ice for analysis in the laboratory of Dr. John Speakman at the Shenzhen Institute of Advanced Technology, Chinese academy of sciences. Isotopes will be measured in benchtop near-infrared isotope gas analyzer, and mean CO2 production will be calculated from isotope ratios using the recently derived equation (Speakman et al 2021: Cell reports medicine). TEE will then be calculated using mean CO2 production using the Weir equation.

  2. Changes of Energy Expenditure Assessed by Chamber

    Time frame: From baseline at week 0 to week 24

    The total energy expenditure in a free living environment is measured using a 24-hour chamber.

  3. Changes of Resting Energy Expenditure

    Time frame: From baseline at week 0 to week 24

    Resting energy expenditure will be measured using indirect calorimetry via a respiratory hood system (Cosmed). The subject attends in the lab after an overnight fast. The person lies down on a flat bed and the hood is placed over their head. Metabolic rate (oxygen consumption and CO2 production) are monitored for 40 minutes. The last 10 minutes is used as the measurement. Calorimeters will be assessed with a turbine test to ensure accuracy of measurements. Validation via an alcohol burn will be performed monthly.

  4. Changes of Physical Activity

    Time frame: From baseline at week 0 to week 24

    Physical activity of the participants will be recorded using GT3X accelerometer worn near the hip for a consecutive period of 14 days. The monitor should not be worn while bathing or swimming. The first day is discarded along with any day where the wear time is less than 12 hours. For a valid measure the goal is to get 2 weekday and 2 weekend days.

Secondary outcomes

  1. Body Weight

    Time frame: From baseline at week 0 to week 24

    Subjects will be asked to fast overnight and weight will be measured using a calibrated Seca body weight scale first thing in the morning on subjects wearing light clothes and no shoes.

  2. Body Mass Index (BMI)

    Time frame: From baseline at week 0 to week 24

    Percent change of body mass index (BMI), as calculated by the formula: body weight in kg divided by height in meters², between baseline and the end of the 24-week randomized drug treatment phase.

  3. Waist and Hip circumferences

    Time frame: From baseline at week 0 to week 24

    Waist and Hip circumferences will be measured using a whole body laser scanner.

  4. Body shape

    Time frame: From baseline at week 0 to week 24

    Body shape will be measured using a whole body laser scanner.

  5. Fat mass

    Time frame: From baseline at week 0 to week 24

    Fat mass will be measured by Magnetic Resonance Imaging (Shanghai united imaging, uMR 790 ).

  6. Far free mass

    Time frame: From baseline at week 0 to week 24

    Fat free mass will be measured by Bioimpedance Analysis (Tanita, MC-980).

  7. Organ sizes

    Time frame: From baseline at week 0 to week 24

    Volumes of the brain, liver, spleen, pancreas, kidneys, subcutaneous and visceral adipose tissue, skeletal muscle in the limbs, trunk and shoulders will be measured by Magnetic Resonance Imaging (Shanghai united imaging, uMR 790 ).

  8. Bone mass

    Time frame: From baseline at week 0 to week 24

    Bone mass will be measured by Dual Energy X-ray Absorptiometry (DEXA) (Hologic)

  9. Changes in Body Composition as Assessed by Body Fat Mass Using Dual Energy X-ray Absorptiometry (DEXA)

    Time frame: From baseline at week 0 to week 24

    Body composition change between baseline and the end of the 24-week randomized drug treatment phase assessed by dual energy x-ray absorptiometry (DEXA) and expressed as the change in fat mass.

  10. Change in energy intake of test meal

    Time frame: From baseline at week 0 to week 24

    The food intake will be assessed objectively by use of a feeding table. The test meal will be provided as lunch, and food types available on the table include staples, vegetables, mushrooms, meat, soy products, desserts, beverages and water. All types of food are unlimited. Food consumption will be recorded continuously by balances concealed under each food dish. The food energy density for each food will be measured by bomb calorimetry in kJ/g, and energy intake will be calculated as the product of the grams of each food eaten multiplied by the respective energy density and then summed, as kJ.

  11. Changes in Fat and Total Calorie Intake Assessed by Free Buffet Meal Analysis

    Time frame: From baseline at week 0 to week 24

    Changes in fat and total calorie intake during free buffet meals assessed at baseline and after 24-weeks of study drug treatment.

  12. Energy intake during ad libitum lunch

    Time frame: From baseline at week 0 to week 24

    The food intake will be assessed objectively by use of a feeding table. The test meal will be provided as lunch, and food types available on the table include staples, vegetables, mushrooms, meat, soy products, desserts, beverages and water. All types of food are unlimited. Food consumption will be recorded continuously by balances concealed under each food dish. The food energy density for each food will be measured by bomb calorimetry in kJ/g, and energy intake will be calculated as the product of the grams of each food eaten multiplied by the respective energy density and then summed, as kJ.

  13. Body temperature from surface temperature of the forehead

    Time frame: From baseline at week 0 to week 24

    Body temperature will be measured before and after feeding using a thermal imaging camera. The camera is directed at the forehead to measure the surface temperature.

  14. Body water

    Time frame: From baseline at week 0 to week 24

    Body water will be measured by deuterium dilution. Subjects will attend in the lab after an overnight fast and provide a baseline urine sample. They will then drink a dose of deuterated water based on their body weight. Three and four hours after dosing a urine sample will be collected to measure the level of deuterium isotope in the body relative to the baseline. This increase allows measurement of the amount of water in the body that diluted the dose.

  15. Overall appetite score (OAS) before and after intake of a standardised meal

    Time frame: From baseline at week 0 to week 24

    give a score from 0 to 100

  16. Mean postprandial rating - Hunger

    Time frame: From baseline at week 0 to week 24

    give a score from 0 to 100, The ends of each line indicate the most extreme sensation respondents have experienced

  17. Mean postprandial rating - Fullness

    Time frame: From baseline at week 0 to week 24

    give a score from 0 to 100, The ends of each line indicate the most extreme sensation respondents have experienced

  18. Mean postprandial rating - Satiety

    Time frame: From baseline at week 0 to week 24

    give a score from 0 to 100, The ends of each line indicate the most extreme sensation respondents have experienced

  19. Mean postprandial rating - Prospective food consumption

    Time frame: From baseline at week 0 to week 24

    give a score from 0 to 100, The ends of each line indicate the most extreme sensation respondents have experienced

  20. Change in physical functioning score

    Time frame: From baseline at week 0 to week 24

    Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.

  21. Change in SF-36: role-physical score

    Time frame: From baseline at week 0 to week 24

    Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.

  22. Change in SF-36: bodily pain score

    Time frame: From baseline at week 0 to week 24

    Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.

  23. Change in SF-36: general health score

    Time frame: From baseline at week 0 to week 24

    Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.

  24. Change in SF-36: vitality score

    Time frame: From baseline at week 0 to week 24

    Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.

  25. Change in SF-36: social functioning score

    Time frame: From baseline at week 0 to week 24

    Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.

  26. Change in SF-36: role-emotional score

    Time frame: From baseline at week 0 to week 24

    Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.

  27. Change in SF-36: mental health score

    Time frame: From baseline at week 0 to week 24

    Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.

  28. Change in SF-36: physical component summary

    Time frame: From baseline at week 0 to week 24

    Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.

  29. Change in SF-36: mental component summary

    Time frame: From baseline at week 0 to week 24

    Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.

  30. Subjects who achieve responder definition value for SF-36 physical functioning score (yes/no)

    Time frame: From baseline at week 0 to week 24

    Number of subjects

  31. Change in HbA1c

    Time frame: From baseline at week 0 to week 24

    mmol /mol

  32. Change in systolic and diastolic blood pressure

    Time frame: From baseline at week 0 to week 24

    Systolic and diastolic blood pressure will be measured using an Omron digital sphygmomanometer, as mmHg.

  33. Blood glucose

    Time frame: From baseline at week 0 to week 24

    Fasting and post-prandial glucose after a standard meal will be recorded by a continuous glucose monitoring system.

  34. Change in fasting serum insulin

    Time frame: From baseline at week 0 to week 24

    mIU/L

  35. Change in lipids: Total cholesterol

    Time frame: From baseline at week 0 to week 24

    mg/dL

  36. Change in lipids: High density lipoprotein (HDL) cholesterol

    Time frame: From baseline at week 0 to week 24

    mg/dL

  37. Change in lipids: Low density lipoprotein (LDL) cholesterol

    Time frame: From baseline at week 0 to week 24

    mg/dL

  38. Change in lipids: Very low density lipoprotein (VLDL) cholesterol

    Time frame: From baseline at week 0 to week 24

    mg/dL

  39. Change in lipids: Free fatty acids (FFA)

    Time frame: From baseline at week 0 to week 24

    mg/dL

  40. Change in lipids: Triglycerides

    Time frame: From baseline at week 0 to week 24

    mg/dL

  41. Change in fatty liver index (FLI) score category

    Time frame: From baseline at week 0 to week 24

    Below 30, equal to or above 30 and below 60, equal to or above 60

  42. Changes in Inflammation Assessed by C-reactive Protein (CRP)

    Time frame: From baseline at week 0 to week 24

    Change in C-reactive protein (CRP) between baseline and the end of the 24-week randomized drug treatment phase

  43. Subjects who have permanently discontinued randomised trial product (yes/no)

    Time frame: From baseline at week 0 to week 24

    Number of subjects

  44. Time to permanent discontinuation of randomised trial product

    Time frame: From baseline at week 0 to week 24

    Weeks

  45. Number of treatment emergent adverse events (TEAEs)

    Time frame: From baseline at week 0 to week 24

    Count

  46. Number of serious adverse events (SAEs)

    Time frame: From baseline at week 0 to week 24

    Count

  47. Change in pulse

    Time frame: From baseline at week 0 to week 24

    Beats per minute (bpm)

  48. Change in amylase

    Time frame: From baseline at week 0 to week 24

    U/L

  49. Change in lipase

    Time frame: From baseline at week 0 to week 24

    U/L

  50. Changes of Circulating Leptin Levels

    Time frame: From baseline at week 0 to week 24

    Change in circulating leptin between baseline and the end of the 24-week randomized drug treatment phase

  51. Circulating hormones

    Time frame: From baseline at week 0 to week 24

    Nurses will collect the blood samples every month. Levels of circulating hormones (including leptin, insulin, ghrelin etc) and metabolic fuels (glycogen, lactate glucose etc) will be measured when fasted and after a standard intervention meal. Levels of circulating hormones in the serum will be measured by ELISA (Bio Tek, Synergy4) in mmol/L.

  52. Microbiome

    Time frame: From baseline at week 0 to week 24

    Abundance of gut microbiome will be from Metagenomic profiling of feces by Illumina.

  53. Metabolites in serum, feces and urine

    Time frame: From baseline at week 0 to week 24

    Abundance of metabolites will be from metabolomic profiling of serum, urine and feces by LC-MS (liquid chromatography-mass spectrometry).

  54. Genetics

    Time frame: From baseline at week 0 to week 24

    Polymorphic variation will be assessed in a panel of SNPs (single nucleotide polymorphism) previously linked to body composition and physical activity using a Mass array sequencer.

    OR The subjects will have their venous blood collected in a fasted state. 4ml of venous blood (BD vacutainer K2 EDTA, BD, USA) will be used to extract genomic DNA (TIANamp Blood DNA kit, TIANGEN, China. QIAamp Midi Blood DNA kit, QIAGEN, Germany) for Single nucleotide polymorphism (SNP) genotyping (Agena MassARRAY, CapitalBio Technology, China).

Sponsors and collaborators

Lead sponsor

Shenzhen Institutes of Advanced Technology ,Chinese Academy of Sciences

Other

Registry information

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Apr 30, 2024
Registry last updated
Jan 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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