Comparative Observation of Metabolic and Pharmacologic Adipose Remodeling With Enhanced Incretin AgonisTs
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Tirzepatide with lifestyle modification, Semaglutide with lifestyle modification.
- Who it may be relevant to
- Registry conditions: Obesity and Metabolic Syndrome. Basic parameters: 20 years — 65 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Taiwan
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Comparative Adipose Tissue and Cardiometabolic System Remodeling by Tirzepatide and Semaglutide: an AI-integrated Multimodal Metabolomics and Translational Mechanistic Study
Overview
This randomized, open label, head to head clinical trial directly compares tirzepatide and semaglutide in adults with obesity and metabolic syndrome (N=120, age 20-65, 1:1 randomization). Participants undergo deep phenotyping at baseline, 6 months, and 12 months, including DXA (regional fat, lean mass, and BMD), MRI PDFF (liver fat), 7 site skinfold thickness, grip strength, fasting biochemistry, and AI processed 12 lead ECGs. Centralized biobanking of serum, plasma, and PBMCs enables targeted and discovery multi omic analyses.
Detailed description
This study is a single-center, randomized, open-label, active-comparator trial designed to characterize the differential effects of tirzepatide and semaglutide on adipose tissue biology and cardiometabolic remodeling over 12 months in adults with obesity and metabolic syndrome. The trial integrates pharmacologic weight-loss therapy with multimodal phenotyping to quantify changes across body composition, hepatic steatosis, metabolic biomarkers, functional strength, and AI-derived electrophysiologic signatures.
The scientific premise is that incretin-based therapies may produce qualitatively distinct patterns of fat loss, ectopic fat mobilization, and cardiometabolic improvement. Tirzepatide, a dual GIP/GLP-1 receptor agonist, may induce greater reductions in visceral adiposity and hepatic fat compared with GLP-1 receptor agonism alone. This trial is designed to directly compare these mechanistic profiles using harmonized imaging, biochemical, and digital phenotyping platforms.
Participants are randomized 1:1 to tirzepatide or semaglutide using a computer-generated permuted block scheme stratified by sex and baseline BMI category. Both interventions follow standard titration schedules and are paired with structured lifestyle counseling to ensure comparable background care. Study visits occur at baseline, 3, 6, and 12 months, with deep phenotyping at baseline, 6, and 12 months.
The phenotyping framework emphasizes regional adiposity, lean mass preservation, hepatic steatosis, and cardiometabolic risk signatures. Whole-body DXA provides quantification of total and regional fat and lean mass, enabling derivation of fat-to-lean mass loss ratios and redistribution indices. Abdominal MRI with proton density fat fraction (PDFF) quantifies liver fat content and abdominal fat compartments. Functional and behavioral assessments-including grip strength and the Chinese version of the Weight-Related Eating Questionnaire-characterize changes in physical function and eating behavior patterns over time.
Fasting biochemical panels measure glycemic indices, lipid metabolism, inflammation, renal and hepatic function, and cardiometabolic biomarkers. Standard 12-lead ECGs are processed through a validated AI pipeline to generate electrophysiologic risk features (e.g., predicted ASCVD risk, ECG-derived heart age), which serve as exploratory digital biomarkers.
A centralized biobanking program supports mechanistic analyses. Serum, plasma, and PBMCs collected at each deep-phenotyping visit are stored under standardized SOPs for targeted and discovery-based metabolomic, proteomic, epigenetic and transcriptomic analyses. These biospecimens will enable downstream investigation of molecular pathways underlying differential treatment responses.
Together, this integrated platform allows for a comprehensive comparison of tirzepatide and semaglutide across structural, metabolic, functional, and molecular domains, providing mechanistic insight into how incretin-based therapies remodel adipose tissue and cardiometabolic physiology.
Interventions
- Drug Tirzepatide with lifestyle modification
Starting at Tirzepatide 2.5 mg weekly and escalated as tolerated to 10 mg along with standardized lifestyle counseling by a dietitian (caloric deficit, physical activity guidance) and written materials. - Drug Semaglutide with lifestyle modification
Starting at Semaglutide 0.25 mg weekly and escalated as tolerated to 2.4 mg along with standardized lifestyle counseling by a dietitian (caloric deficit, physical activity guidance) and written materials.
Primary outcome measures
- Percent change in total body weight from baseline to 6 months. [Time frame: Baseline to 6 months]
- Total fat to lean mass loss ratio (DXA derived) from baseline to 6 months. [Time frame: Baseline to 6 months]
- Change in metabolic syndrome severity Z score from baseline to 6 months. [Time frame: Baseline to 6 months.]
Secondary outcome measures (12)
- Change in waist circumference (cm) [Time frame: Baseline to 6 months and 12 months]
- Change in waist-to-hip ratio (unitless ratio) [Time frame: Baseline to 6 months and 12 months.]
- Change in regional fat mass measured by DXA (grams) [Time frame: Baseline to 6 months and 12 months.]
- Change in regional lean mass measured by DXA (grams) [Time frame: Baseline to 6 months and 12 months]
- Change in 7-site skinfold thickness (mm) [Time frame: Baseline to 6 months and 12 months.]
- Change in liver fat content measured by MRI-PDFF (percentage, %PDFF) [Time frame: Baseline to 6 months and 12 months]
- Change in abdominal visceral fat volume (mL) [Time frame: Baseline to 6 months and 12 months]
- Change in abdominal subcutaneous fat volume (mL) [Time frame: Baseline to 6 months and 12 months]
- Change in systolic and diastolic blood pressure (mmHg) [Time frame: Baseline to 6 months and 12 months]
- Change in fasting lipid profile (mg/dL) [Time frame: Baseline to 6 months and 12 months]
- Change in fasting glucose (mg/dL) [Time frame: Baseline to 6 and 12 months]
- Change in hsCRP (mg/L) [Time frame: Baseline to 6 and 12 months]
Eligibility criteria
Inclusion criteria
- Age 20-65 years.
- BMI ≥27 kg/m² with metabolic syndrome (ATP III or IDF criteria).
- Stable background medications (antihypertensives, statins, etc.) for ≥3 months.
- Able and willing to provide informed consent and comply with study procedures.
Exclusion criteria
- History of diabetes; history of pancreatitis; personal/family history of medullary thyroid carcinoma or MEN2.
- eGFR <30 mL/min/1.73 m², decompensated liver disease, NYHA class III-IV heart failure.
- Recent (<3 months) acute coronary syndrome, stroke, or coronary revascularization.
- Current use of GLP 1RA, tirzepatide, or other incretin based therapies within 3 months.
- Contraindications to MRI or DXA (e.g., metal implants incompatible with MRI, pregnancy).
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Taiwan · 1 center
- Tri-Service General Hospital — Taipei
Identifiers
NCT: NCT07589322 · C202505161