Protein supplements with semaglutide and a calorie-restricted diet for weight loss

An Intervention Study Investigating Effect of Dietary Protein Supplementation on Body Weight and Metabolic Homeostasis

This will test whether adding daily protein supplements to semaglutide plus a calorie-restricted diet helps adults with overweight or obesity lose more weight, preserve muscle, and reduce weight regain.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 140 (estimated)
• Ages: 20 Years to 50 Years
• Sex: All
• Sponsor: Chinese Academy of Sciences (Government)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06989203 on ClinicalTrials.gov

What this trial studies

This randomized, parallel-group trial will enroll adults with overweight or obesity and assign them to one of three 3-month interventions: a calorie-restricted balanced diet (CRD) alone, CRD plus semaglutide, or CRD plus semaglutide with 30 g/day of protein supplementation, followed by 6 months of follow-up. Investigators will measure weight loss, body composition, energy and glucose-lipid metabolism, muscle loss, and weight regain using body composition scans, metabolic testing including a mixed-macronutrient tolerance test, continuous glucose monitoring, activity/sleep monitoring, imaging, and biological samples (stool, urine, blood). The study will also analyze modifiers of response such as obesity phenotype, gut microbiota, genetics, and lifestyle to inform personalized intervention strategies. About 120 overweight/obese and 20 normal-weight participants will be recruited at Tongde Hospital of Zhejiang Province with 1:1:1 randomization among the three intervention arms.

Who should consider this trial

Good fit: Adults aged 20–50 with BMI ≥ 24 kg/m² (overweight or obese) who meet indications for semaglutide and are willing to follow a calorie-restricted diet and study procedures are ideal candidates.

Not a fit: People who are normal-weight, have medical contraindications to semaglutide, have the metabolic abnormalities excluded by the trial, or who cannot adhere to the diet or supplement regimen may not receive benefit from this intervention.

Why it matters

Potential benefit: If successful, adding dietary protein to semaglutide and a calorie-restricted diet could increase weight loss, reduce muscle loss during treatment, and lower the risk of regaining weight.

How similar studies have performed: Semaglutide and other GLP-1 receptor agonists have reliably produced substantial weight loss in prior trials and protein supplementation can limit muscle loss during calorie restriction, but combining protein supplementation specifically with GLP‑1RA therapy to prevent weight regain is relatively novel and not yet widely tested.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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):
  1. Waist circumference ≥ 90 cm for men or ≥ 85 cm for women.
  2. Fasting glucose ≥ 6.1 mmol/L or 2-hour postprandial glucose ≥ 7.8 mmol/L, or a confirmed diagnosis of diabetes.
  3. Systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 85 mmHg, or currently under antihypertensive treatment.
  4. 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.

  2\. Overweight or obese (BMI ≥ 24 kg/m²):
  1. Fasting plasma glucose \> 11.1 mmol/L or HbA1c \> 9%, or previously diagnosed diabetes, or currently using insulin or any antidiabetic medication.
  2. Blood pressure ≥ 160/100 mmHg, or clinically diagnosed stage 2 or stage 3 (moderate or severe) hypertension, or currently under antihypertensive treatment.
  3. 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.

Where this trial is running

Hangzhou, Zhejiang

• Tongde Hospital of Zhejiang Province — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Xu Lin, PhD — Institute for Nutritional Sciecnes, CAS; Hangzhou Institute for Advanced Study, UCAS
• Study coordinator: Wanhui Kang, PhD

Conditions Obesity; Weight Loss; Protein Supplementation