ObesityNCT06989203
Protein Supplementation Intervention on Body Weight
A study testing General lifestyle and nutritional education, Calorie-restricted balanced diet and semaglutide in people with Obesity and Weight Loss, run by Chinese Academy of Sciences at 1 site in China.
Trial summary
This study is a randomized clinical trail with a parallel design, involving 120 overweight/obese (body-mass index, BMI ≥ 24 kg/m²) participants and 20 normal-weight participants. Read more about this study
- Who is it for?
- Ages 20 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity, Weight Loss, Protein Supplementation
- What is being tested?
- General lifestyle and nutritional education, Calorie-restricted balanced diet and semaglutide
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 1 siteChina
- Study dates
- 10 Jun 2025to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 20 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Aged 20 to 50 years.
- Normal-weight participants: 18.5 kg/m² ≤ Body Mass Index (BMI) < 24 kg/m².
- Overweight or obese participants:
- BMI ≥ 28 kg/m², or 24 kg/m² ≤ BMI < 28 kg/m² and a clinical diagnosis meeting semaglutide treatment indications (e.g., hyperglycemia, hypertension, dyslipidemia, fatty liver, obstructive sleep apnea, cardiovascular disease, etc.).
- Willingness to participate in this study and provide signed informed consent.
Who cannot join
- Abnormal metabolic indicators (meeting any one of the following criteria is grounds for exclusion):
- 1. Normal weight (18.5 kg/m² ≤ BMI < 24 kg/m²):
- Waist circumference ≥ 90 cm for men or ≥ 85 cm for women.
- Fasting glucose ≥ 6.1 mmol/L or 2-hour postprandial glucose ≥ 7.8 mmol/L, or a confirmed diagnosis of diabetes.
- Systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 85 mmHg, or currently under antihypertensive treatment.
- Fasting triglycerides (TG) ≥ 1.7 mmol/L; high-density lipoprotein cholesterol (HDL-C) < 0.9 mmol/L in men or < 1.0 mmol/L in women.
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- 2. Overweight or obese (BMI ≥ 24 kg/m²):
- Fasting plasma glucose > 11.1 mmol/L or HbA1c > 9%, or previously diagnosed diabetes, or currently using insulin or any antidiabetic medication.
- Blood pressure ≥ 160/100 mmHg, or clinically diagnosed stage 2 or stage 3 (moderate or severe) hypertension, or currently under antihypertensive treatment.
- Use of lipid-lowering drugs (e.g., fibrates, bile acid sequestrants, statins, PCSK9 inhibitors) within the past 3 months, or TG ≥ 5.7 mmol/L, or LDL ≥ 4.9 mmol/L.
- Pregnancy or lactation.
- Self-reported weight change of more than 5 kg within the 90 days prior to screening.
- Use of antibiotics, antimicrobials, or anti-inflammatory/analgesic salicylates (e.g., aspirin) within the 3 months prior to screening for 3 days or more.
- Use of estrogen therapy or other hormonal medications within the past 6 months.
- Use of GLP-1 receptor agonists or probiotics within the past 3 months.
- Heavy alcohol consumption (females > 40 g/day, approximately 250 mL of huangjiu [yellow rice wine], or 1000 mL of beer, or 100 mL of liquor per day; males > 80 g/day).
- Severe liver or kidney dysfunction (ALT, AST, or serum creatinine exceeding 3 times the upper limit of normal, UACR ≥ 30 mg/g, or eGFR < 60 mL/min).
- Gastrointestinal diseases affecting digestion and absorption (e.g., severe diarrhea, severe constipation, severe inflammatory bowel disease, peptic ulcer, gallstones, cholecystitis).
- Underwent surgery within the past year (excluding appendectomy or hernia repair).
- Severe cardiovascular or cerebrovascular diseases (e.g., heart failure, myocardial infarction, stroke, acute myocarditis, severe arrhythmia, or receiving interventional therapy).
- Presence of metallic implants such as a cardiac stent or pacemaker.
- Cancer or having received radiation or chemotherapy within the past 5 years.
- Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia, or a personal history of hyperthyroidism or hypothyroidism.
- Chronic or acute pancreatitis.
- Positive hepatitis B surface antigen (HBsAg), active tuberculosis, HIV, or other infectious diseases.
- Currently participating in another clinical study or having done so within the past 3 months.
- Claustrophobia.
- Any psychiatric disorder such as attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, or epilepsy (including current use of antiepileptic medications), or use of antidepressant medications.
- Inability to read, write, operate a smartphone, or perform daily activities independently.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Tongde Hospital of Zhejiang Province
Hangzhou, Zhejiang, 310024
Wanhui Kang, PhD, +86 86081210, kangwanhui@ucas.ac.cn
Xu Lin
About this study
Official title: An Intervention Study Investigating Effect of Dietary Protein Supplementation on Body Weight and Metabolic Homeostasis
This study is a randomized clinical trail with a parallel design, involving 120 overweight/obese (body-mass index, BMI ≥ 24 kg/m²) participants and 20 normal-weight participants. Overweight/obese participants will be randomly allocated to one of three groups: 1) calorie restricted balanced diet (CRD)group; 2) CRD + semaglutide group; or 3) CRD + segaglutide with protein supplementation. Through a 3-month weight loss intervention and 6-month follow-up, this study aims to investigate the effects of dietary protein supplementation combined with semaglutide on weight loss, energy and glucose and lipid metabolism, muscle loss, and weight regain. Additionally, the study will explore key factors affecting intervention efficacy, including obesity phenotypes, gut microbiota profiles, genetic backgrounds, and lifestyle factors, to provide evidence for optimizing individualized intervention strategies.
Read the detailed description
The primary objective of this study is to determine whether adding dietary protein supplementation to GLP 1 receptor agonist (GLP-1RA, semaglutide) therapy enhances weight loss efficacy, improves energy and glucose-lipid metabolism, mitigates muscle loss, and prevents weight regain. Investigators will also explore key modifiers of treatment response-including obesity phenotype, gut microbiota composition, genetic background, and lifestyle factors-to provide an evidence base for personalized interventions.
Investigators will enroll 120 adults with overweight or obesity (BMI ≥ 24 kg/m²) and randomly assign them (1 : 1 : 1) to one of three 3 month interventions:
- CRD: calorie restricted balanced diet;
- CRD + GLP-1RA: CRD plus semaglutide;
- CRD + GLP-1RA + HP: CRD plus semaglutide and 30 g/day of dietary protein supplement.
Baseline and post intervention assessments will include questionnaires; evaluations of diet, physical activity, and sleep patterns; physical examination (height, weight, waist and hip circumference, blood pressure, pulse); body composition analysis; hepatic fat and fibrosis imaging; facial skin phenotyping; 14 day continuous glucose monitoring; 14 day accelerometer based sleep and activity monitoring; stool and urine collection; and a mixed-macronutrient tolerance test (MMTT) performed in a metabolic chamber.
During the MMTT, participants consume a standardized beverage containing 126.5 g glucose, 30.67 g fat, and 34.5 g protein. Blood samples are collected at 0, 0.5, 1, 2, 3, 4, and 5 hours to characterize post prandial dynamics of energy metabolism, routine clinical biomarkers, and metabolomic profiles. Throughout the intervention, dietary intake is recorded via a mobile application, and body weight changes are tracked with an application linked smart scale.
Six months after the intervention, participants undergo follow up assessments (identical questionnaires, physical examination, fasting laboratory tests for glucose, insulin, HbA1c, lipids, and liver and renal function indices) and provide a stool sample.
To provide a healthy reference, Investigators will additionally recruit 20 normal weight adults who will receive weight maintenance dietary counseling for 3 months and undergo pre and post intervention MMTTs in the metabolic chamber. These data will help determine whether the metabolic homeostasis of overweight/obese participants after the three interventions approaches that of healthy individuals and will aid in identifying determinants of inter individual variability.
The study protocol has been approved by the Ethics Committee of Zhejiang Provincial Tongde Hospital.
- Conditions
- Obesity, Weight Loss, Protein Supplementation
- Being tested
- General lifestyle and nutritional education, Calorie-restricted balanced diet, semaglutide, Dietary protein supplementation
- Medical subject headings
- Obesity, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
General lifestyle and nutritional educationBehavioural
Participants will receive dietary advice, behavior guidance and nutritional and lifestyle education based on dietary guidelines.
Calorie-restricted balanced dietBehavioural
Participants will receive dietary advice, behavior guidance and nutritional and lifestyle education by dietitian and physicians. APP-connected wearable devices will be utilized to monitor their dietary intakes and APP-connected scale will be used to monitor their weight changes during interventions.
semaglutideDrug
Participants will receive semaglutide as medically prescribed
Dietary protein supplementationDietary supplement
participants will receive 30 g/day of dietary protein supplementation
| Study group | Role | What they receive |
|---|---|---|
| CRD | Placebo comparator | They will receive calorie restricted balanced diet and placebo Receives: Behavioral: Calorie-restricted balanced diet |
| CRD+GLP-1RA | Active comparator | They will receive calorie restricted balanced diet and semaglutide Receives: Behavioral: Calorie-restricted balanced diet; Drug: semaglutide |
| CRD+GLP-1RA+HP | Experimental | They will receive calorie restricted balanced diet, semaglutide, and 30g/day of dietary protein supplementation Receives: Behavioral: Calorie-restricted balanced diet; Drug: semaglutide; Dietary Supplement: Dietary protein supplementation |
| Healthy Comparators | Other | They will receive general lifestyle and nutritional education. Receives: Behavioral: General lifestyle and nutritional education |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Body Weight (kg) from Baseline to Week 12
The change between the baseline and after 12-week intervention. Weight will be assessed using a Seca-255 scale (ScalesGalore).
Measured: Baseline and Week 12
Secondary outcomes (37)
Change in Energy Expenditure Rate (kcal/minute) from Baseline to Week 12
The change between the baseline and after 12-week intervention. Energy expenditure rate (kcal/minute) will be assessed with a whole-room indirect calorimeter.
Measured: Baseline and Week 12
Change in Respiratory Quotient from Baseline to Week 12
The change between the baseline and after 12-week intervention. Respiratory quotient will be assessed with a whole-room indirect calorimeter.
Measured: Baseline and Week 12
Change in Fat Oxidation Rate (g/minute) from Baseline to Week 12
The change between the baseline and after 12-week intervention. Fat oxidation rate (g/minute) will be assessed with a whole-room indirect calorimeter.
Measured: Baseline and Week 12
Change in Carbohydrate Oxidation Rate (g/minute) from Baseline to Week 12
The change between the baseline and after 12-week intervention. Carbohydrate oxidation rate (g/minute) will be assessed with a whole-room indirect calorimeter.
Measured: Baseline and Week 12
Change in Waist Circumference (cm) from Baseline to Week 12
The change between the baseline and after 12-week intervention. Waist circumference will be assessed using a Seca-201tape (ScalesGalore).
Measured: Baseline and Week 12
Change in Hip Circumference (cm) from Baseline to Week 12
The change between the baseline and after 12-week intervention. Hip circumference will be assessed using a Seca-201 tape (ScalesGalore).
Measured: Baseline and Week 12
Change in Fat-free Mass (kg) From Baseline to Week 12
Absolute change in whole-body fat-free mass measured by dual-energy X-ray absorptiometry (DXA; GE Lunar iDXA).
Values at Week 12 will be subtracted from baseline; a positive value indicates an increase in fat-free mass.
Measured: Baseline (Week 0) and Week 12
Change in Fat Mass (kg) From Baseline to Week 12
Absolute change in whole-body fat mass measured by dual-energy X-ray absorptiometry (DXA; GE Lunar iDXA).
Values at Week 12 minus baseline; a positive value indicates an increase in fat mass.
Measured: Baseline (Week 0) and Week 12
Change in Controlled Attenuation Parameter (CAP, dB/m) from Baseline to Week 12
The change between the baseline and after 12-week intervention. CAP will be assessed using FibroScane (Echosens). The median CAP value of 10 valid measurements will be used (IQR ≤ 30%). Reported value = Week 12 CAP minus baseline CAP; positive values indicate increased hepatic steatosis.
Measured: Baseline and Week 12
Change in Systolic Blood Pressure (mmHg) from Baseline to Week 12
The change in systolic blood pressure between the baseline and after 12-week intervention. Systolic blood pressure will be assessed with an electronic blood pressure monitor (Omron J750).
Measured: Baseline and Week 12
Change in Diastolic Blood Pressure (mmHg) from Baseline to Week 12
The change in diastolic blood pressure between the baseline and after 12-week intervention. Diastolic blood pressure will be assessed with an electronic blood pressure monitor (Omron J750).
Measured: Baseline and Week 12
Change in Heart Rate (beats/minute) from Baseline to Week 12
The change in heart rate between the baseline and after 12-week intervention. Heart rate will be assessed using Omron J750.
Measured: Baseline and Week 12
Change in Fasting Glucose (mmol/L) from Baseline to Week 12
The change of fasting glucose between the baseline and after 12-week intervention. Glucose will be measured using a hexokinase enzymatic assay.
Measured: Baseline and Week 12
Change in Glucose Incremental AUC (mmol·min/L) from Baseline to Week 12
Venous blood will be collected at 0, 30, 60, 120, 180, 240, and 300 min during an oral mixed-meal tolerance test (MMTT). Glucose will be measured using a hexokinase enzymatic assay. Incremental area under the concentration-time curve (iAUC) will be calculated via the trapezoidal rule after subtracting the fasting value. Reported value = Week 12 iAUC - baseline iAUC; positive numbers indicate an increase.
Measured: Baseline and Week 12
Change in HbA1c (%) from Baseline to Week 12
The change between the baseline and after 12-week intervention. HbA1c will be assessed using high-performance liquid chromatography
Measured: Baseline and Week 12
Change in Fasting Insulin (µIU/mL) from Baseline to Weel 12
The change of fasting insulin between the baseline and after 12-week intervention. Insulin will be measured using an electrochemiluminescence assay.
Measured: Baseline and Week 12
Change in Insulin Incremental AUC (µIU·min/mL) from Baseline to Weel 12
Venous blood will be collected at 0, 30, 60, 120, 180, 240, and 300 min during an MMTT. Insulin will be measured using an electrochemiluminescence assay. Incremental area under the concentration-time curve (iAUC) will be calculated via the trapezoidal rule after subtracting the fasting value. Reported value = Week 12 iAUC - baseline iAUC; positive numbers indicate an increase.
Measured: Baseline and Week 12
Change in Fasting C-peptide (ng/mL) from Baseline to Week 12
The change of fasting C-peptide between the baseline and after 12-week intervention. C-peptide will be measured using an electrochemiluminescence assay.
Measured: Baseline and Week 12
Change in C-peptide Incremental AUC (ng·min/mL) from Baseline to Week 12
Venous blood will be collected at 0, 30, 60, 120, 180, 240, and 300 min during an MMTT. C-peptide will be measured using an electrochemiluminescence assay. Incremental area under the concentration-time curve (iAUC) will be calculated via the trapezoidal rule after subtracting the fasting value. Reported value = Week 12 iAUC - baseline iAUC; positive numbers indicate an increase.
Measured: Baseline and Week 12
Change in Mean 24-h Glucose (mg/dL) from Baseline to Week 12
The change between the baseline and after 12-week intervention. Mean 24-h glucose will be assessed using Continuous Glucose Monitoring (FreeStyle Libre 2, Abbott) for 14 consecutive days.
Measured: Baseline and Week 12
Change in Glucose Coefficient of Variation (CV, %) from Baseline to Week 12
The change between the baseline and after 12-week intervention. Glucose CV) will be calculated as (SD/mean) × 100 % from continuous glucose monitoring (FreeStyle Libre 2, Abbott). Participants will wear the sensor for 14 consecutive days at each time point.
Measured: Baseline and Week 12
Change in Fasting Serum Triglycerides (mmol/L) from Baseline to Week 12
The change of fasting serum triglycerides between the baseline and after 12-week intervention. Serum triglycerides will be quantified using an enzymatic colorimetric assay.
Measured: Baseline and Week 12
Change in Triglyceride Incremental AUC (mmol·min/L) from Baseline to Week 12
Venous blood will be collected at 0, 30, 60, 120, 180, 240, and 300 min during an MMTT. Triglyceride will be measured using an enzymatic colorimetric assay. Incremental area under the concentration-time curve (iAUC) will be calculated via the trapezoidal rule after subtracting the fasting value. Reported value = Week 12 iAUC - baseline iAUC; positive numbers indicate an increase.
Measured: Baseline and Week 12
Change in Fasting Serum Total Cholesterol (mmol/L) from Baseline to Week 12
The change of fasting total cholesterol between the baseline and after 12-week lifestyle intervention. Total cholesterol will be quantified in serum using an enzymatic colorimetric assay.
Measured: Baseline and Week 12
Change in Total Cholesterol Incremental AUC (mmol·min/L) from Baseline at 12 Weeks
Venous blood will be collected at 0, 30, 60, 120, 180, 240, and 300 min during an MMTT. Total cholesterol will be measured using an enzymatic colorimetric assay. Incremental area under the concentration-time curve (iAUC) will be calculated via the trapezoidal rule after subtracting the fasting value. Reported value = Week 12 iAUC - baseline iAUC; positive numbers indicate an increase.
Measured: Baseline and Week 12
Change in Fasting Serum High-Density Lipoprotein Cholesterol (HDL-C, mmol/L) from Baseline to Week 12
The change of fasting HDL-C between the baseline and after 12-week lifestyle intervention. HDL-C will be quantified in serum using an enzymatic colorimetric assay.
Measured: Baseline and Week 12
Change in HDL-c Incremental AUC (mmol·min/L) from Baseline to 12 Weeks
Venous blood will be collected at 0, 30, 60, 120, 180, 240, and 300 min during an MMTT. HDL-c will be measured using an enzymatic colorimetric assay. Incremental area under the concentration-time curve (iAUC) will be calculated via the trapezoidal rule after subtracting the fasting value. Reported value = Week 12 iAUC - baseline iAUC; positive numbers indicate an increase.
Measured: Baseline and Week 12
Change in Fasting Serum Low-Density Lipoprotein Cholesterol (LDL-C, mmol/L) from Baseline to Week 12
The change of fasting LDL-C between the baseline and after 12-week lifestyle intervention. LDL-C will be quantified in serum using an enzymatic colorimetric assay.
Measured: Baseline and Week 12
Change in LDL-c Incremental AUC (mmol·min/L) from Baseline to 12 Weeks
Venous blood will be collected at 0, 30, 60, 120, 180, 240, and 300 min during an MMTT. LDL-c will be measured using an enzymatic colorimetric assay. Incremental area under the concentration-time curve (iAUC) will be calculated via the trapezoidal rule after subtracting the fasting value. Reported value = Week 12 iAUC - baseline iAUC; positive numbers indicate an increase.
Measured: Baseline and Week 12
Change in GLP-1 Incremental AUC (pg·min/mL) from Baseline to Week 12
Venous blood will be collected at 0, 30, 60, 120, 180, 240, and 300 min during an MMTT. GLP-1 will be quantified using a high-sensitivity ELISA . Incremental area under the concentration-time curve (iAUC) will be calculated via the trapezoidal rule after subtracting the fasting value.
Measured: Baseline and Week 12
Change in GIP Incremental AUC (pg·min/mL) from Baseline to Week 12
Venous blood will be collected at 0, 30, 60, 120, 180, 240, and 300 min during an MMTT. GIP will be quantified using a high-sensitivity ELISA . Incremental area under the concentration-time curve (iAUC) will be calculated via the trapezoidal rule after subtracting the fasting value.
Measured: Baseline and Week 12
Change in Ghrelin Incremental AUC (pg·min/mL) from Baseline to Week 12
Venous blood will be collected at 0, 30, 60, 120, 180, 240, and 300 min during an MMTT. Ghrelin will be quantified using a high-sensitivity ELISA . Incremental area under the concentration-time curve (iAUC) will be calculated via the trapezoidal rule after subtracting the fasting value.
Measured: Baseline and Week 12
Change in Shannon Diversity Index From Baseline to Week 12
Fecal DNA will be extracted and subjected to shotgun metagenomic sequencing on an Illumina NovaSeq 6000 (2 × 150 bp; ≥6 Gb per sample). Reads will be taxonomically profiled using MetaPhlAn 4.0. The Shannon diversity index will be calculated for each sample.
Measured: Baseline and Week 12
Change in Relative Abundance of Akkermansia muciniphila (%) From Baseline to Week 12
Same sequencing workflow as above. Relative abundance (% of total classified reads) of A. muciniphila will be extracted from MetaPhlAn output. Reported value = Week 12 minus baseline abundance.
Measured: Baseline and Week 12
Single nucleotide polymorphism (SNPs)
Mutations at specific sites will be detected using a genotyping microarray.
Measured: Baseline
Change in body weight from Week 12 to 6 months post-intervention
The hange from the end of intervention (Week 12) to 6 months post-intervention. Weight will be assessed using Seca-255 scale (ScalesGalore).
Measured: Post-intervention 6 months
Change in Facial Skin Phenotype from Baseline to Week 12
The change between the baseline and after 12-week lifestyle intervention.Facial skin phenotype will assessed using Meitueve 3D skin analysis system (Meitu, China).
Measured: Baseline and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2025
- Study start10 Jun 2025
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese Academy of Sciences
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Xu Lin, Chinese Academy of Sciences
- Investigators
- Xu Lin, PhD, Principal investigator, Institute for Nutritional Sciecnes, CAS; Hangzhou Institute for Advanced Study, UCAS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06989203
- Sponsor's protocol ID
- HIAS-PSITBW-202504
- Status last verified
- Mar 2026
- First submitted
- 6 May 2025
- Last updated
- 17 Mar 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Intervention Study Investigating Effect of Dietary Protein Supplementation on Body Weight and Metabolic Homeostasis
- ClinicalTrials.gov ID
- NCT06989203
- Acronym / sponsor ID
- HIAS-PSITBW-202504
- Conditions
- Obesity, Weight Loss, Protein Supplementation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Chinese Academy of SciencesOther government
- Study start
- 10 Jun 2025 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 25 May 2025 (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.
This study is a randomized clinical trail with a parallel design, involving 120 overweight/obese (body-mass index, BMI ≥ 24 kg/m²) participants and 20 normal-weight participants. Overweight/obese participants will be randomly allocated to one of three groups: 1) calorie restricted balanced diet (CRD)group; 2) CRD + semaglutide group; or 3) CRD + segaglutide with protein supplementation. Through a 3-month weight loss intervention and 6-month follow-up, this study aims to investigate the effects of dietary protein supplementation combined with semaglutide on weight loss, energy and glucose and lipid metabolism, muscle loss, and weight regain. Additionally, the study will explore key factors affecting intervention efficacy, including obesity phenotypes, gut microbiota profiles, genetic backgrounds, and lifestyle factors, to provide evidence for optimizing individualized intervention strategies.
Detailed description
The primary objective of this study is to determine whether adding dietary protein supplementation to GLP 1 receptor agonist (GLP-1RA, semaglutide) therapy enhances weight loss efficacy, improves energy and glucose-lipid metabolism, mitigates muscle loss, and prevents weight regain. Investigators will also explore key modifiers of treatment response-including obesity phenotype, gut microbiota composition, genetic background, and lifestyle factors-to provide an evidence base for personalized interventions.
Investigators will enroll 120 adults with overweight or obesity (BMI ≥ 24 kg/m²) and randomly assign them (1 : 1 : 1) to one of three 3 month interventions:
- CRD: calorie restricted balanced diet;
- CRD + GLP-1RA: CRD plus semaglutide;
- CRD + GLP-1RA + HP: CRD plus semaglutide and 30 g/day of dietary protein supplement.
Baseline and post intervention assessments will include questionnaires; evaluations of diet, physical activity, and sleep patterns; physical examination (height, weight, waist and hip circumference, blood pressure, pulse); body composition analysis; hepatic fat and fibrosis imaging; facial skin phenotyping; 14 day continuous glucose monitoring; 14 day accelerometer based sleep and activity monitoring; stool and urine collection; and a mixed-macronutrient tolerance test (MMTT) performed in a metabolic chamber.
During the MMTT, participants consume a standardized beverage containing 126.5 g glucose, 30.67 g fat, and 34.5 g protein. Blood samples are collected at 0, 0.5, 1, 2, 3, 4, and 5 hours to characterize post prandial dynamics of energy metabolism, routine clinical biomarkers, and metabolomic profiles. Throughout the intervention, dietary intake is recorded via a mobile application, and body weight changes are tracked with an application linked smart scale.
Six months after the intervention, participants undergo follow up assessments (identical questionnaires, physical examination, fasting laboratory tests for glucose, insulin, HbA1c, lipids, and liver and renal function indices) and provide a stool sample.
To provide a healthy reference, Investigators will additionally recruit 20 normal weight adults who will receive weight maintenance dietary counseling for 3 months and undergo pre and post intervention MMTTs in the metabolic chamber. These data will help determine whether the metabolic homeostasis of overweight/obese participants after the three interventions approaches that of healthy individuals and will aid in identifying determinants of inter individual variability.
The study protocol has been approved by the Ethics Committee of Zhejiang Provincial Tongde Hospital.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| CRD | Placebo comparator | Behavioral: Calorie-restricted balanced dietThey will receive calorie restricted balanced diet and placebo |
| CRD+GLP-1RA | Active comparator | Behavioral: Calorie-restricted balanced diet, Drug: semaglutideThey will receive calorie restricted balanced diet and semaglutide |
| CRD+GLP-1RA+HP | Experimental | Behavioral: Calorie-restricted balanced diet, Drug: semaglutide, Dietary Supplement: Dietary protein supplementationThey will receive calorie restricted balanced diet, semaglutide, and 30g/day of dietary protein supplementation |
| Healthy Comparators | Other | Behavioral: General lifestyle and nutritional educationThey will receive general lifestyle and nutritional education. |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Aged 20 to 50 years.
- Normal-weight participants: 18.5 kg/m² ≤ Body Mass Index (BMI) < 24 kg/m².
- Overweight or obese participants:
- BMI ≥ 28 kg/m², or 24 kg/m² ≤ BMI < 28 kg/m² and a clinical diagnosis meeting semaglutide treatment indications (e.g., hyperglycemia, hypertension, dyslipidemia, fatty liver, obstructive sleep apnea, cardiovascular disease, etc.).
- Willingness to participate in this study and provide signed informed consent.
Key exclusion criteria (29 listed)
- Abnormal metabolic indicators (meeting any one of the following criteria is grounds for exclusion):
- Pregnancy or lactation.
- Self-reported weight change of more than 5 kg within the 90 days prior to screening.
- Use of antibiotics, antimicrobials, or anti-inflammatory/analgesic salicylates (e.g., aspirin) within the 3 months prior to screening for 3 days or more.
- Use of estrogen therapy or other hormonal medications within the past 6 months.
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 |
|---|---|---|
| General lifestyle and nutritional educationParticipants will receive dietary advice, behavior guidance and nutritional and lifestyle education based on dietary guidelines. | Behavioural | Healthy Comparators |
| Calorie-restricted balanced dietParticipants will receive dietary advice, behavior guidance and nutritional and lifestyle education by dietitian and physicians. APP-connected wearable devices will be utilized to monitor their dietary intakes and APP-connected scale will be used to monitor their weight changes during interventions. | Behavioural | CRD, CRD+GLP-1RA, CRD+GLP-1RA+HP |
| semaglutideParticipants will receive semaglutide as medically prescribed | Drug | CRD+GLP-1RA, CRD+GLP-1RA+HP |
| Dietary protein supplementationparticipants will receive 30 g/day of dietary protein supplementation | Dietary supplement | CRD+GLP-1RA+HP |
Primary outcome
Change in Body Weight (kg) from Baseline to Week 12
Time frame: Baseline and Week 12
The change between the baseline and after 12-week intervention. Weight will be assessed using a Seca-255 scale (ScalesGalore).
37 secondary outcomes
Change in Energy Expenditure Rate (kcal/minute) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Respiratory Quotient from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Fat Oxidation Rate (g/minute) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Carbohydrate Oxidation Rate (g/minute) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Waist Circumference (cm) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Hip Circumference (cm) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Fat-free Mass (kg) From Baseline to Week 12
Time frame: Baseline (Week 0) and Week 12
Change in Fat Mass (kg) From Baseline to Week 12
Time frame: Baseline (Week 0) and Week 12
Change in Controlled Attenuation Parameter (CAP, dB/m) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Systolic Blood Pressure (mmHg) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Diastolic Blood Pressure (mmHg) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Heart Rate (beats/minute) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Fasting Glucose (mmol/L) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Glucose Incremental AUC (mmol·min/L) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in HbA1c (%) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Fasting Insulin (µIU/mL) from Baseline to Weel 12
Time frame: Baseline and Week 12
Change in Insulin Incremental AUC (µIU·min/mL) from Baseline to Weel 12
Time frame: Baseline and Week 12
Change in Fasting C-peptide (ng/mL) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in C-peptide Incremental AUC (ng·min/mL) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Mean 24-h Glucose (mg/dL) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Glucose Coefficient of Variation (CV, %) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Fasting Serum Triglycerides (mmol/L) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Triglyceride Incremental AUC (mmol·min/L) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Fasting Serum Total Cholesterol (mmol/L) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Total Cholesterol Incremental AUC (mmol·min/L) from Baseline at 12 Weeks
Time frame: Baseline and Week 12
Change in Fasting Serum High-Density Lipoprotein Cholesterol (HDL-C, mmol/L) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in HDL-c Incremental AUC (mmol·min/L) from Baseline to 12 Weeks
Time frame: Baseline and Week 12
Change in Fasting Serum Low-Density Lipoprotein Cholesterol (LDL-C, mmol/L) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in LDL-c Incremental AUC (mmol·min/L) from Baseline to 12 Weeks
Time frame: Baseline and Week 12
Change in GLP-1 Incremental AUC (pg·min/mL) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in GIP Incremental AUC (pg·min/mL) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Ghrelin Incremental AUC (pg·min/mL) from Baseline to Week 12
Time frame: Baseline and Week 12
Change in Shannon Diversity Index From Baseline to Week 12
Time frame: Baseline and Week 12
Change in Relative Abundance of Akkermansia muciniphila (%) From Baseline to Week 12
Time frame: Baseline and Week 12
Single nucleotide polymorphism (SNPs)
Time frame: Baseline
Change in body weight from Week 12 to 6 months post-intervention
Time frame: Post-intervention 6 months
Change in Facial Skin Phenotype from Baseline to Week 12
Time frame: Baseline and Week 12
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2026.
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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.
Xu Lin, PhD principal investigator
Institute for Nutritional Sciecnes, CAS; Hangzhou Institute for Advanced Study, UCAS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing General lifestyle and nutritional education, Calorie-restricted balanced diet and semaglutide in people with Obesity and Weight Loss, run by Chinese Academy of Sciences at 1 site in China.
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 5 inclusion and 29 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: looking for participants now, as of the sponsor's last update on 17 Mar 2026. 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 China. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wanhui Kang, PhD (+86 86081210, kangwanhui@ucas.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Body Weight (kg) from Baseline to Week 12 (time frame: Baseline and Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Mar 2026.