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

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.

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