Effect of Tirzepatide on Brown Adipose Tissue in Obesity (TABFAT)

Effect of Tirzepatide-Induced Weight Loss on Adipose Tissue in Obesity

This study is testing whether a new anti-obesity medicine called tirzepatide can increase the activity of special fat cells in the body that help burn energy. These fat cells are known as brown and beige fat. The study includes women with obesity and will last 24 weeks.

Participants will receive either tirzepatide or a placebo (a look-alike injection with no active drug). Researchers will measure the amount and activity of brown fat using medical imaging (PET/CT, MRI, and thermal camera), and examine fat tissue samples to look for changes in gene activity and structure that show beige fat activation.

The study will also evaluate how these fat changes affect body weight, energy use, hormone levels, blood sugar, and other health markers. The goal is to learn whether tirzepatide helps improve metabolism by increasing energy-burning fat in addition to reducing appetite.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity
• Intervention / Treatment: Drug: Tirzepatide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Female sex
• Age between 18 and 50 years
• BMI between 30 kg/m² and 40 kg/m² at pre-screening
• Prior comprehensive non-pharmacological and non-surgical management of obesity, including a history of at least 12 months of intensive lifestyle intervention with a maximum weight reduction of less than 5%
• Stable body weight within the three months preceding study enrollment (defined as weight fluctuations within 5%)
• No prior pharmacological or surgical interventions for obesity
• Euthyroid state
• Eumenorrhea or Oligomenorrhea
• Ability to comprehend the study objectives and procedures
• Willingness to provide informed consent and to comply with the study protocol, including the use of highly effective contraception during the study period, with signed consent and agreement provided in duplicate
• Commitment to use highly reliable contraception and absence of plans for pregnancy within the 8 months following enrollment

Exclusion Criteria:

• Pregnancy or lactation
• Postmenopausal
• Amenorea
• Type 2 diabetes
• Reliance on natural contraception methods
• Non-compliance with previous therapeutic regimens
• Personal history of malignancy
• Personal or family history of medullary thyroid carcinoma
• Personal history of pancreatitis
• Personal history of cholelithiasis
• Personal history of major depressive episodes or suicidal ideation
• Personal history of acute coronary events or hemodynamically significant coronary artery disease
• Psychiatric disorders
• Current treatment with sympathomimetics or sympatholytics
• Excessive alcohol consumption

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo will be administered via subcutaneous injection once weekly using pens that are visually indistinguishable from those used for tirzepatide. Dose escalation will follow the same schedule (2.5 mg-equivalent increments every 4 weeks) to preserve blinding integrity.
Experimental: Tirzepatide	Drug: Tirzepatide; Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. It will be administered via subcutaneous injection once weekly in a dose-titration scheme: starting at 2.5 mg, and increased every 4 weeks by 2.5 mg up to a maximum of 15 mg, based on tolerability. The medication will be supplied in prefilled pens identical in appearance to placebo pens.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brown Adipose Tissue Activity and Volume	Assessed using 18F-FDG-PET/CT, magnetic resonance imaging (MRI), and infrared thermography. Outcome measured as change in mean standardized uptake value, supraclavicular skin temperature, and BAT volume in predefined anatomical regions (supraclavicular and cervical areas) between baseline and after 24 weeks of treatment.	Baseline to Week 24
Change in Molecular Markers of Browning in Subcutaneous White Adipose Tissue	Measured as changes in the expression levels of uncoupling protein 1 (UCP1) and other browning-associated genes (via RT-PCR and RNA sequencing) in subcutaneous white adipose tissue (WAT) biopsies. Additionally, assessed through histomorphometric analysis of adipocyte phenotype, including the proportion of multilocular (plurivacuolar) adipocytes, immune cell infiltration, and microvascular density, to characterize tissue remodeling indicative of beige adipocyte induction.	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation Between Different BAT Assessment Methods	Comparative analysis between 18F-FDG-PET/CT, MRI fat fraction, and infrared thermography for assessing BAT activity and volume.	Baseline and Week 24
Change in Resting Energy Expenditure	Measured by indirect calorimetry using a portable metabolic analyzer. Outcome reported as absolute change in REE (kcal/day).	Baseline to Week 24
Association Between Changes in Resting Energy Expenditure, Metabolic Health Markers, and Thermogenic Adipose Tissue	Assessed by evaluating correlations between changes in resting energy expenditure (REE, measured by indirect calorimetry), metabolic health parameters (including glucose metabolism, insulin sensitivity indices, lipid profile, and hormonal markers), body composition changes, and alterations in thermogenic adipose tissue activity and volume (as measured by 18F-FDG-PET/CT, MRI, and thermography). This outcome aims to determine the interrelationship between metabolic adaptations and thermogenic fat activation following tirzepatide treatment.	Baseline to Week 24
Association Between Resting Energy Expenditure, Metabolic Health Markers, and Thermogenic Adipose Tissue	Assessed by evaluating correlations between anthropometric data, resting energy expenditure (REE, measured by indirect calorimetry), metabolic health parameters (including glucose metabolism, insulin sensitivity indices, lipid profile, and hormonal markers), body composition, and thermogenic adipose tissue activity and volume (as measured by 18F-FDG-PET/CT, MRI, and thermography). This outcome aims to determine variables that correlate with pre-treatment thermogenic adipose tissue quantity and activity.	Baseline

Collaborators and Investigators

• Sponsor: University Medical Centre Ljubljana

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2025
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 18, 2025
• First Submitted That Met QC Criteria: March 18, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): May 15, 2025
• Last Update Submitted That Met QC Criteria: May 14, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: obesity; energy expenditure; brown adipose tissue; tirzepatide; beige adipose tissue; adipose tissue browning
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Obesity; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Tirzepatide
• Other Study ID Numbers: 0120-56/2024-2711-7

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) to be shared will include demographic data, basic clinical measurements, body composition assessment, laboratory results, imaging data, resting energy expenditure measurements, molecular data and histological features from subcutaneous adipose tissue biopsies. All shared data will be fully de-identified, and no directly identifiable personal information will be included.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No