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Comparative Observation of Metabolic and Pharmacologic Adipose Remodeling With Enhanced Incretin AgonisTs (COMPARE-AT)

10 mei 2026 bijgewerkt door: Feng-Chih Kuo, Tri-Service General Hospital

Comparative Adipose Tissue and Cardiometabolic System Remodeling by Tirzepatide and Semaglutide: an AI-integrated Multimodal Metabolomics and Translational Mechanistic Study

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.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Geschat)

120

Fase

  • Niet toepasbaar

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

  • Naam: Feng-Chih Kuo, M.D., Ph.D.
  • Telefoonnummer: 12687 886-2-87923311
  • E-mail: shoummie@hotmail.com

Studie Locaties

  • Taiwan
      • Taipei, Taiwan, 114202
        • Werving
        • Tri-Service General Hospital
        • Contact:

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Beschrijving

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).

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Actieve vergelijker: Tirzepatide arm
starting at 2.5 mg weekly and escalated every month (5.0 mg, 7.5 mg to 10 mg) as tolerated
Geneesmiddel: 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.
Actieve vergelijker: Semaglutide arm
starting at 0.25 mg weekly and escalated every month (0.5 mg, 1.0 mg, 1.7 mg to 2.4 mg) as tolerated
Geneesmiddel: 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.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Percent change in total body weight from baseline to 6 months.
Tijdsspanne: Baseline to 6 months
Baseline to 6 months
Total fat to lean mass loss ratio (DXA derived) from baseline to 6 months.
Tijdsspanne: Baseline to 6 months
Baseline to 6 months
Change in metabolic syndrome severity Z score from baseline to 6 months.
Tijdsspanne: Baseline to 6 months.
Baseline to 6 months.

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Change in waist circumference (cm)
Tijdsspanne: Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in waist-to-hip ratio (unitless ratio)
Tijdsspanne: Baseline to 6 months and 12 months.
Baseline to 6 months and 12 months.
Change in regional fat mass measured by DXA (grams)
Tijdsspanne: Baseline to 6 months and 12 months.
Baseline to 6 months and 12 months.
Change in regional lean mass measured by DXA (grams)
Tijdsspanne: Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in 7-site skinfold thickness (mm)
Tijdsspanne: Baseline to 6 months and 12 months.
Baseline to 6 months and 12 months.
Change in liver fat content measured by MRI-PDFF (percentage, %PDFF)
Tijdsspanne: Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in abdominal visceral fat volume (mL)
Tijdsspanne: Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in abdominal subcutaneous fat volume (mL)
Tijdsspanne: Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in systolic and diastolic blood pressure (mmHg)
Tijdsspanne: Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in fasting lipid profile (mg/dL)
Tijdsspanne: Baseline to 6 months and 12 months
Lipid profile includes total cholesterol, LDL-C, HDL-C and Triglycerides
Baseline to 6 months and 12 months
Change in fasting glucose (mg/dL)
Tijdsspanne: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in hsCRP (mg/L)
Tijdsspanne: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in insulin sensitivity (HOMA-IR, unitless)
Tijdsspanne: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in β-cell function (HOMA-β, percentage, %)
Tijdsspanne: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in AI-ECG predicted ASCVD risk score (percentage, %)
Tijdsspanne: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in ECG-derived heart age (years)
Tijdsspanne: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in AI-ECG diabetes risk index (HbA1c, percentage, %)
Tijdsspanne: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in estimated 10-year ASCVD risk (percentage, %)
Tijdsspanne: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in bone mineral density (g/cm²)
Tijdsspanne: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in serum P1NP (ng/mL)
Tijdsspanne: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in serum CTX-1 (ng/mL)
Tijdsspanne: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in fasting plasma metabolomics profile (relative abundance units)
Tijdsspanne: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in fasting plasma proteomics profile (relative abundance units)
Tijdsspanne: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in microRNA expression signatures (normalized expression units)
Tijdsspanne: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in RNA-seq transcriptomic signatures (normalized counts, e.g., TPM)
Tijdsspanne: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in epigenetic methylation signatures (Methylation, percentage, %)
Tijdsspanne: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in depressive symptoms (scale score)
Tijdsspanne: Baseline to 6 and 12 months
Instrument: e.g., PHQ-9
Baseline to 6 and 12 months
Change in sleep quality (scale score)
Tijdsspanne: Baseline to 6 and 12 months
Instrument: e.g., PSQI
Baseline to 6 and 12 months
Change in quality of life (scale score)
Tijdsspanne: Baseline to 6 and 12 months
Instrument: e.g., EQ-5D or SF-36
Baseline to 6 and 12 months
Change in eating behavior (WREQ-C total and subscale scores)
Tijdsspanne: Baseline to 3, 6, and 12 months
Baseline to 3, 6, and 12 months

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Tri-Service General Hospital

Medewerkers

National Science and Technology Council, Taiwan

Onderzoekers

  • Studie directeur: Feng-Chih Kuo, M.D., Ph.D., Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan.

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

31 maart 2026

Primaire voltooiing (Geschat)

30 september 2028

Studie voltooiing (Geschat)

30 september 2029

Studieregistratiedata

Eerst ingediend

1 mei 2026

Eerst ingediend dat voldeed aan de QC-criteria

10 mei 2026

Eerst geplaatst (Werkelijk)

15 mei 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

15 mei 2026

Laatste update ingediend die voldeed aan QC-criteria

10 mei 2026

Laatst geverifieerd

1 mei 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • C202505161

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Beschrijving IPD-plan

It is still ongoing and can not be shared before the final analysis.

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

product vervaardigd in en geëxporteerd uit de V.S.

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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