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

Official title

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

Overview

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.

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.

Interventions

• 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).

Primary outcome measures

• 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 [Time frame: Baseline to 24 weeks]

Secondary outcome measures (12)

• Change in waist circumference [Time frame: Baseline to 24 weeks]
• Change in body weight (kg) [Time frame: Baseline to 24 weeks]
• Change in Body Mass Index (BMI) [Time frame: Baseline to 24 weeks]
• Change in HbA1c (%) [Time frame: Baseline to 24 weeks]
• Change in fasting glucose (mg/dL) [Time frame: Baseline to 24 weeks]
• Change in HOMA-IR [Time frame: Baseline to 24 weeks]
• Change in fasting lipids (LDL-C, HDL-C, TG, TC) [Time frame: Baseline to 24 weeks]
• Change in body composition by BIA (fat mass, lean mass, skeletal muscle mass) [Time frame: Baseline to 24 weeks]
• Change in liver fat fraction (MRI-PDFF, %) [Time frame: Baseline to 24 weeks]
• Change in liver stiffness by MRE (kPa) [Time frame: Baseline to 24 weeks]
• Change in adipokines (adiponectin, leptin, NEFA) [Time frame: Baseline to 24 weeks]
• Change in hsCRP [Time frame: Baseline to 24 weeks]

Eligibility criteria

Inclusion criteria

• Age 20-70 years at the time of enrollment
• Initiating semaglutide (Wegovy) treatment for obesity (newly starting treatment)
• 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)
• Ability and willingness to provide written informed consent

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

South Korea · 2 centers

• Hallym University Dongtan Sacred Heart Hospital — Hwaseong-si
• Seoul National University Bundang Hospital — Seongnam-si

Identifiers

NCT: NCT07621640 · 2026-04-009 · RS-2026-25483260

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗