Probiotic or semaglutide plus diet to reduce body weight

An Interventional Study Investigating the Effects of Probiotics on Body Weight and Metabolic Homeostasis

This project will test whether adding a probiotic (Lactobacillus paracasei LC-19) or semaglutide to a calorie-restricted diet helps overweight adults lose weight and improve blood sugar and lipid levels.

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: NCT06989177 on ClinicalTrials.gov

What this trial studies

In a randomized controlled design, 120 overweight or obese adults (BMI ≥ 24 kg/m²) will be assigned to 12 weeks of an energy-restricted diet and lifestyle program plus either placebo, the probiotic Lactobacillus paracasei LC-19, or semaglutide injections, while 20 normal-weight participants will follow weight-maintenance guidance. Before and after the intervention participants will undergo a standardized mixed-meal tolerance test and repeated measurements of energy metabolism, clinical biomarkers, metabolomics, gut microbiota, and genetic signatures to characterize metabolic homeostasis. The protocol compares weight loss, changes in glucose and lipid metabolism, side effects, adverse events, and short-term weight regain across interventions. The study will also explore biological and clinical factors that predict who responds best to each intervention to inform individualized strategies.

Who should consider this trial

Good fit: Adults aged 20–50 with overweight or obesity (BMI ≥ 24 kg/m²) who can commit to a 12-week calorie-restricted diet and study visits are the intended participants, with some overweight participants required to meet semaglutide treatment indications.

Not a fit: People outside the 20–50 age range, those with uncontrolled metabolic abnormalities or diabetes, or those unable or unwilling to follow the diet, injection, or follow-up schedule are unlikely to benefit from or be eligible for this protocol.

Why it matters

Potential benefit: If successful, the trial could identify a simpler or more targeted way to help people lose weight and improve glucose and lipid control, and guide personalized treatment choices.

How similar studies have performed: GLP-1 receptor agonists like semaglutide have demonstrated substantial, reproducible weight loss in multiple large trials, whereas probiotic approaches have shown mixed and less consistent results to date.

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

• Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences — 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; Homeostasis; Weight Loss; Probiotic Intervention