Fecal Microbiota Transplantation (FMT) Combined With Calorie-Restricted Diet and Semaglutide in Patients With Obesity and Type 2 Diabetes

Effects of Comprehensive Intervention With Fecal Microbiota Transplantation Versus Conventional Treatment on Body Weight and Metabolism in Patients With Obesity Complicated by Type 2 Diabetes Mellitus: A Randomized Controlled Trial

Investigation of the efficacy of fecal microbiota transplantation added to calorie-restricted diet and semaglutide versus calorie-restricted diet and semaglutide alone for weight loss and metabolic improvement in patients with moderate to severe obesity and type 2 diabetes mellitus.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity Type 2 Diabetes Mellitus
• Intervention / Treatment: Biological: Fecal microbiota transplantation (FMT); Drug: Semaglutide (1 Mg Dose); Behavioral: Calorie-restricted diet

Detailed Description

This study is designed as a single-center, randomized, open-label, parallel-controlled trial. A total of 20 patients with moderate to severe obesity and T2DM (BMI 30-40 kg/m²) whose T2DM duration is less than one year will be enrolled, and randomly assigned to either the intervention group (FMT + ccalorie-restricted diet + semaglutide) or the control group (calorie-restricted diet + semaglutide). The intervention period will be 24 weeks. The primary endpoint is the percentage change in body weight from baseline to post-intervention. Secondary endpoints include the proportion of patients achieving a >5% weight loss, as well as metabolic parameters such as fasting blood glucose, lipid profile, glycated hemoglobin, visceral fat parameters, and gut microbiota diversity (Shannon/Simpson index).

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yunfeng Shen, Ph.D; Phone Number: 0755-83982222; Email: shenyf26@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518033
      • Eighth Affiliated Hospital, Sun Yat-sen University
      • Contact: Yunfeng Shen, Ph.D; Phone Number: 0755-83982222; Email: shenyf26@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-60 years;
2. Body mass index (BMI) ≥30 kg/m² and <40 kg/m²;
3. Duration of type 2 diabetes mellitus <1 year;
4. Non-smoker or smoking cessation >3 months;
5. Voluntary signed informed consent with commitment to complete the entire study.

Exclusion Criteria:

1. Complicated with severe hepatic or renal insufficiency (alanine aminotransferase/aspartate aminotransferase [ALT/AST] >3 times the upper limit of normal, or estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m²);
2. Inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), or other organic intestinal diseases; autoimmune diseases, malignancies, or active infections;
3. Medication and intervention exclusions: Use of α-glucosidase inhibitors, antibiotics, proton pump inhibitors (PPIs), or probiotics/prebiotics within the past 3 months; bariatric surgery within the past 6 months; long-term use of immunosuppressants or glucocorticoids;
4. Others: Pregnant or lactating women; currently participating in other clinical trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; A comprehensive intervention combining fecal microbiota transplantation, calorie-restricted diet, and glucagon-like peptide-1 receptor agonist.	Biological: Fecal microbiota transplantation (FMT); Donor Selection: Healthy lean donors with BMI <23 kg/m² will be selected following rigorous health screening. Capsule Preparation: Donor fecal samples will be homogenized, filtered to remove debris, lyophilized, and encapsulated in enteric-coated capsules. Oral FMT capsule dosage: 10 capsules per dose, once daily, for 6 consecutive days each month.; Other Names: FMT; Drug: Semaglutide (1 Mg Dose); Semaglutide 1.0 mg subcutaneous injection once weekly; Other Names: GLP-1 receptor agonist; glucagon-like peptide-1 receptor agonist; Behavioral: Calorie-restricted diet; Daily caloric intake will be individualized based on physical activity level: 25 kcal/kg/day for individuals with light-to-moderate physical activity and 30 kcal/kg/day for those with heavy physical activity.; Other Names: CRD
Active Comparator: Control group; Conventional treatment with calorie-restricted diet and glucagon-like peptide-1 receptor agonist.	Drug: Semaglutide (1 Mg Dose); Semaglutide 1.0 mg subcutaneous injection once weekly; Other Names: GLP-1 receptor agonist; glucagon-like peptide-1 receptor agonist; Behavioral: Calorie-restricted diet; Daily caloric intake will be individualized based on physical activity level: 25 kcal/kg/day for individuals with light-to-moderate physical activity and 30 kcal/kg/day for those with heavy physical activity.; Other Names: CRD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change in body weight	The percentage change in body weight from baseline to follow-up visit (week 24) is presented. Body weight (kg) will be measured using a calibrated electronic scale operated by research personnel who have undergone standardized training.	From enrollment to the end of treatment at 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of participants achieving ≥5% body weight reduction	The percentage of participants who achieved ≥5% weight reduction from baseline to follow-up visit (week 24) is presented. Body weight (kg) will be measured using a calibrated electronic scale operated by research personnel who have undergone standardized training.	From enrollment to the end of treatment at 24 weeks
Change in glycated hemoglobin (HbA1c)	Change in glycated hemoglobin (HbA1c) from baseline to week 12 and week 24 is presented. HbA1c (%) values will be retrieved from the hospital's electronic medical record system.	Baseline, Week 12, and Week 24
Change in fasting insulin	Change in fasting insulin from baseline to week 12 and week 24 is presented. Fasting insulin (μU/mL) values will be retrieved from the hospital's electronic medical record system.	Baseline, Week 12, and Week 24
Change in fasting plasma glucose	Change in fasting plasma glucose from baseline to week 12 and week 24 is presented. Fasting plasma glucose (mmol/L) values will be retrieved from the hospital's electronic medical record system.	Baseline, Week 12, and Week 24
Change in total cholesterol	Change in total cholesterol from baseline to week 12 and week 24 is presented. Total cholesterol (mmol/L) values will be retrieved from the hospital's electronic medical record system.	Baseline, Week 12, and Week 24
Change in low-density lipoprotein cholesterol	Change in low-density lipoprotein cholesterol from baseline to week 12 and week 24 is presented. Low-density lipoprotein cholesterol (mmol/L) will be retrieved from the hospital's electronic medical record system.	Baseline, Week 12, and Week 24
Change in high-density lipoprotein cholesterol	Change in high-density lipoprotein cholesterol from baseline to week 12 and week 24 is presented. High-density lipoprotein cholesterol (mmol/L) will be retrieved from the hospital's electronic medical record system.	Baseline, Week 12, and Week 24
Change in triglycerides	Change in triglycerides from baseline to week 12 and week 24 is presented. Triglycerides (mmol/L) values will be retrieved from the hospital's electronic medical record system.	Baseline, Week 12, and Week 24
Change in uric acid	Change in uric acid from baseline to week 12 and week 24 is presented. Uric acid (μmol/L) values will be retrieved from the hospital's electronic medical record system.	Baseline, Week 12, and Week 24
Change in urinary albumin-to-creatinine ratio	Change in urinary albumin-to-creatinine ratio from baseline to week 12 and week 24 is presented. The albumin-to-creatinine ratio is defined as urinary albumin (mg) divided by urinary creatinine (g). Albumin-to-creatinine ratio (mg/g) values will be retrieved from the hospital's electronic medical record system.	Baseline, Week 12, and Week 24
Change in high-sensitivity C-reactive protein	Change in high-sensitivity C-reactive protein from baseline to week 12 and week 24 is presented. High-sensitivity C-reactive protein (mg/dL) values will be retrieved from the hospital's electronic medical record system.	Baseline, Week 12, and Week 24
Change in gut microbiota diversity indices	Change in gut microbiota diversity indices (such as Shannon diversity index and Simpson diversity index) from baseline to week 12 and week 24 is presented. The gut microbiota diversity indices will be derived from metagenomic sequencing data.	Baseline, Week 12, and Week 24
Change in fecal short-chain fatty acid concentrations	Change in fecal short-chain fatty acid concentrations from baseline to week 12 and week 24 is presented. Fecal short-chain fatty acid concentrations (µmol/g wet feces) will be measured by gas chromatography.	Baseline, Week 12, and Week 24
Change in systolic blood pressure	Change in systolic blood pressure from baseline to week 12 and week 24 is presented. Systolic blood pressure (mmHg) values will be retrieved from the hospital's electronic medical record system.	Baseline, Week 12, and Week 24
Change in diastolic blood pressure	Change in diastolic blood pressure from baseline to week 12 and week 24 is presented. Diastolic blood pressure (mmHg) values will be retrieved from the hospital's electronic medical record system.	Baseline, Week 12, and Week 24
Change in body mass index	Change in body mass index (BMI) from baseline to week 12 and week 24 is presented. BMI is calculated using the formula: BMI = weight (kg) / [height (m)]². Height and weight will be measured using a stadiometer and calibrated electronic scale, respectively, operated by research personnel who have undergone standardized training.	Baseline, Week 12, and Week 24
Change in waist circumference	Change in waist circumference from baseline to week 12 and week 24 is presented. Waist circumference (cm) will be measured using a non-elastic measuring tape operated by research personnel who have undergone standardized training.	Baseline, Week 12, and Week 24
Change in muscle mass	Change in muscle mass from baseline to week 12 and week 24 is presented. Muscle mass (kg) will be measured using an InBody body composition analyzer operated by research personnel who have undergone standardized training.	Baseline, Week 12, and Week 24
Change in body fat percentage	Change in body fat percentage from baseline to week 12 and week 24 is presented. Body fat percentage (%) will be measured using an InBody body composition analyzer operated by research personnel who have undergone standardized training.	Baseline, Week 12, and Week 24
Change in visceral fat area	Change in visceral fat area from baseline to week 12 and week 24 is presented. Visceral fat area (cm²) will be measured using a bioelectrical impedance analyzer operated by research personnel who have undergone standardized training.	Baseline, Week 12, and Week 24

Collaborators and Investigators

• Sponsor: Eighth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2026
• Primary Completion (Estimated): January 30, 2027
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: April 9, 2026
• First Submitted That Met QC Criteria: May 13, 2026
• First Posted (Actual): May 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Obesity; Semaglutide; Type 2 diabetes mellitus; Fecal microbiota transplantation; Calorie-restricted diet
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Diabetes Mellitus, Type 2; Therapeutics; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Diet Therapy; Nutrition Therapy; Diet; Biological Therapy; Energy Intake; semaglutide; Fecal Microbiota Transplantation; Caloric Restriction
• Other Study ID Numbers: 2025-183-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No