Brown Adipose Tissue as a Mechanistic Determinant of Semaglutide Treatment Response in Obesity (BAT-Sema Study) (BAT-Sema)

Brown Adipose Tissue as a Mechanistic Determinant of GLP-1 Receptor Agonist Treatment Response in Adults With Obesity: A Multicenter Prospective Cohort Study Using ¹⁸FDG-PET/CT and Cold Stimulation Protocol

This study investigates whether the activity of brown adipose tissue (BAT) - a special type of fat that burns energy as heat - can predict how well individuals with obesity respond to semaglutide (Wegovy), a once-weekly injectable weight loss medication. Participants who are starting semaglutide treatment will undergo ¹⁸FDG-PET/CT imaging before and after 24 weeks of treatment. Prior to each PET/CT scan, participants will wear a water-circulating cooling vest to activate BAT. By measuring BAT activity at baseline and comparing it with the degree of weight loss and metabolic improvement at 24 weeks, the investigators aim to identify BAT as a predictive biomarker for personalized obesity treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity; Metabolic Syndrome; Brown Adipose Tissue
• Intervention / Treatment: Drug: Semaglutide (Wegovy®); Procedure: ¹⁸FDG-PET/CT with cold stimulation; Procedure: Liver MRI (PDFF + MRE)

Detailed Description

Despite the remarkable efficacy of semaglutide (GLP-1 receptor agonist) in treating obesity, considerable individual variation in treatment response remains unexplained. Brown adipose tissue (BAT) is a metabolically active thermogenic organ that has been implicated in energy expenditure, insulin sensitivity, and cardiometabolic health. We hypothesize that baseline BAT activity, as measured by ¹⁸FDG-PET/CT following individualized cold stimulation, is a mechanistic determinant of semaglutide treatment response in adults with obesity without diabetes.

This multicenter prospective cohort study will enroll 80 adults (40 per site: Hallym University Dongtan Sacred Heart Hospital and Seoul National University Bundang Hospital) with BMI ≥27 kg/m² plus obesity-related comorbidity, or BMI ≥30 kg/m², who are initiating semaglutide therapy. ¹⁸FDG-PET/CT with standardized cold stimulation (water-circulating cooling vest, starting at 16°C, individualized to prevent shivering) will be performed at baseline (V1) and 24 weeks (V7). BAT activity (SUVmax, SUVmean, BAT volume, total metabolic activity) will be quantified per BARCIST 1.0 criteria. Liver fat fraction (MRI-PDFF) and liver stiffness (MR elastography) will be assessed as secondary endpoints. Correlations between baseline BAT parameters and treatment outcomes (% body weight loss, metabolic biomarker changes) will be analyzed.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hun Jee Choe Hallym University Dongtan Sacred Heart Hospital, MD, PhD; Phone Number: +82-31-8086-2869; Email: hunjeechoe@gmail.com
• Study Contact Backup: Name: Hye Jeong Lee Hallym University Dongtan Sacred Heart Hospital, CRC; Phone Number: +82-10-4694-3886; Email: geumzzogi@naver.com

Study Locations

• South Korea
  • Gyeonggi-do
    • Hwaseong-si, Gyeonggi-do, South Korea, 18450
      • Hallym University Dongtan Sacred Heart Hospital
      • Contact: Hun Jee Choe Hallym University Dongtan Sacred Heart Hospital, MD, PhD; Phone Number: +82-10-9493-5703; Email: hunjeechoe@gmail.com
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Seoul National University Bundang Hospital
      • Contact: Soo Lim Seoul National University Bundang Hospital, MD, PhD; Phone Number: +82-10-9766-2706; Email: limsoo@snu.ac.kr
      • Contact: Soo Lim Seoul National University Bundang Hospital, MD, PhD; Phone Number: +82-010-9766-2706; Email: limsoo@snu.ac.kr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 20-70 years at the time of enrollment
2. Initiating semaglutide (Wegovy) treatment for obesity (newly starting treatment)

3. BMI ≥ 27 kg/m² with at least one weight-related comorbidity:

   • Hypertension (SBP ≥130 or DBP ≥80 mmHg, or on antihypertensive medication)
   • Dyslipidemia (LDL-C ≥130, TG ≥150, or low HDL-C, or on lipid-lowering medication)
   • Non-alcoholic fatty liver disease (NAFLD/MASLD, confirmed by imaging or ALT/AST ≥1.5× ULN)
   • Obstructive sleep apnea (AHI ≥5/hr or clinically diagnosed)
   • Established cardiovascular disease (CAD, stroke, PAD)
   • Obesity-related osteoarthritis of knee or hip with functional impairment OR BMI ≥ 30 kg/m² (regardless of comorbidity)
4. Ability and willingness to provide written informed consent

Exclusion Criteria:

1. Diagnosis of type 1 or type 2 diabetes mellitus
2. History of neck surgery or radiation therapy to the neck
3. Use of anti-obesity medications within 1 month prior to enrollment, or current use of beta-adrenergic blocking agents
4. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2)
5. Active malignancy, severe renal disease (eGFR <30 mL/min/1.73m²), severe hepatic disease, or other severe endocrine disorders
6. Pregnancy or breastfeeding
7. Severe psychiatric illness or cognitive impairment precluding informed consent
8. Contraindication to MRI (pacemaker, cochlear implant, non-MRI-compatible implants)
9. Severe claustrophobia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Semaglutide + BAT Evaluation; Adults with obesity initiating semaglutide (0.25 mg → 2.4 mg over 20 weeks, maintained for 4 weeks; total 24 weeks). At baseline and 24 weeks, ¹⁸FDG-PET/CT with individualized cold stimulation (water-circulating cooling vest at 16°C, 60 minutes) and liver MRI (PDFF + MRE) are performed.

Drug: Semaglutide (Wegovy®); Once-weekly subcutaneous injection, titrated from 0.25 mg to 2.4 mg over 20 weeks per standard protocol. Standard of care treatment for obesity.; Procedure: ¹⁸FDG-PET/CT with cold stimulation; Whole-body ¹⁸FDG-PET/CT (5.18 MBq/kg, max 370 MBq) after 60-minute individualized cold stimulation using a water-circulating cooling vest (Polar Products Arctic Chiller, starting 16°C). Performed at baseline (V1) and 24 weeks (V7). BAT activity quantified per BARCIST 1.0.; Procedure: Liver MRI (PDFF + MRE); Hepatic proton density fat fraction (MRI-PDFF) and liver stiffness by MR elastography (MRE) using Siemens MAGNETOM Vida 3T. Performed at baseline (V1) and 24 weeks (V7).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between baseline BAT metabolic activity (SUVmean and BAT volume on ¹⁸FDG-PET/CT) and percentage body weight loss at 24 weeks of semaglutide treatment	: Pearson (or Spearman) correlation coefficient between baseline BAT parameters (SUVmean, BAT volume, total metabolic activity per BARCIST 1.0) and % body weight loss after 24 weeks of semaglutide therapy (0.25 mg escalated to 2.4 mg).	Baseline to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in waist circumference		Baseline to 24 weeks
Change in body weight (kg)		Baseline to 24 weeks
Change in Body Mass Index (BMI)		Baseline to 24 weeks
Change in HbA1c (%)		Baseline to 24 weeks
Change in fasting glucose (mg/dL)		Baseline to 24 weeks
Change in HOMA-IR		Baseline to 24 weeks
Change in fasting lipids (LDL-C, HDL-C, TG, TC)		Baseline to 24 weeks
Change in body composition by BIA (fat mass, lean mass, skeletal muscle mass)		Baseline to 24 weeks
Change in liver fat fraction (MRI-PDFF, %)		Baseline to 24 weeks
Change in liver stiffness by MRE (kPa)		Baseline to 24 weeks
Change in adipokines (adiponectin, leptin, NEFA)		Baseline to 24 weeks
Change in hsCRP		Baseline to 24 weeks
BAT-positive rate based on SUVmax at baseline	The percentage of participants determined as brown adipose tissue (BAT)-positive, defined by a maximum standardized uptake value (SUVmax) of 1.5 or higher ($\ge 1.5$) at baseline.	Baseline
Change in Quality of life using the Impact of Weight on Quality of Life-Lite Clinical Trials (IWQOL-Lite-CT) total score	The Impact of Weight on Quality of Life-Lite Clinical Trials (IWQOL-Lite-CT) is a self-report questionnaire used to assess the quality of life in individuals with obesity. The total score ranges from a minimum of 0 to a maximum of 100, where higher scores indicate a better outcome (better quality of life).	Baseline to 24 weeks
Change in Quality of Life using the Short Form-36 Health Survey Version 2 (SF-36v2) domain scores	The Short Form-36 Health Survey Version 2 (SF-36v2) is a 36-item questionnaire measuring health-related quality of life across 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Each domain score ranges from a minimum of 0 to a maximum of 100, where higher scores indicate a better outcome (better health status or higher quality of life).	Baseline to 24 weeks
Change in BAT activity (SUVmax, SUVmean, BAT volume, TMA) from baseline to 24 weeks		Baseline to 24 weeks
BAT-positive rate based on CT Hounsfield Units (HU) at baseline	The percentage of participants determined as brown adipose tissue (BAT)-positive, defined by Computed Tomography Hounsfield Units (CT HU) within the range of $-250$ to $-50$ at baseline.	Baseline

Collaborators and Investigators

• Sponsor: Hallym University
• Collaborators: Hallym University Dongtan Sacred Heart Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2031

Study Registration Dates

• First Submitted: May 20, 2026
• First Submitted That Met QC Criteria: May 27, 2026
• First Posted (Actual): June 2, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Biomarker; Obesity; Semaglutide; Weight loss; FDG-PET/CT; GLP-1 receptor agonist; BAT; Brown adipose tissue; PDFF
• Additional Relevant MeSH Terms: Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Body Weight Changes; Glucose Metabolism Disorders; Insulin Resistance; Hyperinsulinism; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Weight Loss; Metabolic Syndrome; semaglutide
• Other Study ID Numbers: 2026-04-009; RS-2026-25483260 (Other Grant/Funding Number: National Research Foundation of Korea)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared publicly. De-identified aggregate results will be published in peer-reviewed journals

Drug and device information, study documents

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