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

10. mai 2026 oppdatert av: 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.

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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

Intervensjonell

Registrering (Antatt)

120

Fase

  • Ikke aktuelt

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studiesteder

  • Taiwan
      • Taipei, Taiwan, 114202
        • Rekruttering
        • Tri-Service General Hospital
        • Ta kontakt med:

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

  • Voksen
  • Eldre voksen

Tar imot friske frivillige

Nei

Beskrivelse

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).

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Aktiv komparator: Tirzepatide arm
starting at 2.5 mg weekly and escalated every month (5.0 mg, 7.5 mg to 10 mg) as tolerated
Legemiddel: 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.
Aktiv komparator: 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
Legemiddel: 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.

Hva måler studien?

Primære resultatmål

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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Change in waist circumference (cm)
Tidsramme: Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in waist-to-hip ratio (unitless ratio)
Tidsramme: Baseline to 6 months and 12 months.
Baseline to 6 months and 12 months.
Change in regional fat mass measured by DXA (grams)
Tidsramme: Baseline to 6 months and 12 months.
Baseline to 6 months and 12 months.
Change in regional lean mass measured by DXA (grams)
Tidsramme: Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in 7-site skinfold thickness (mm)
Tidsramme: 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)
Tidsramme: Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in abdominal visceral fat volume (mL)
Tidsramme: Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in abdominal subcutaneous fat volume (mL)
Tidsramme: Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in systolic and diastolic blood pressure (mmHg)
Tidsramme: Baseline to 6 months and 12 months
Baseline to 6 months and 12 months
Change in fasting lipid profile (mg/dL)
Tidsramme: 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)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in hsCRP (mg/L)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in insulin sensitivity (HOMA-IR, unitless)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in β-cell function (HOMA-β, percentage, %)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in AI-ECG predicted ASCVD risk score (percentage, %)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in ECG-derived heart age (years)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in AI-ECG diabetes risk index (HbA1c, percentage, %)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in estimated 10-year ASCVD risk (percentage, %)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in bone mineral density (g/cm²)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in serum P1NP (ng/mL)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in serum CTX-1 (ng/mL)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in fasting plasma metabolomics profile (relative abundance units)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in fasting plasma proteomics profile (relative abundance units)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in microRNA expression signatures (normalized expression units)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in RNA-seq transcriptomic signatures (normalized counts, e.g., TPM)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in epigenetic methylation signatures (Methylation, percentage, %)
Tidsramme: Baseline to 6 and 12 months
Baseline to 6 and 12 months
Change in depressive symptoms (scale score)
Tidsramme: Baseline to 6 and 12 months
Instrument: e.g., PHQ-9
Baseline to 6 and 12 months
Change in sleep quality (scale score)
Tidsramme: Baseline to 6 and 12 months
Instrument: e.g., PSQI
Baseline to 6 and 12 months
Change in quality of life (scale score)
Tidsramme: 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)
Tidsramme: Baseline to 3, 6, and 12 months
Baseline to 3, 6, and 12 months

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Tri-Service General Hospital

Samarbeidspartnere

National Science and Technology Council, Taiwan

Etterforskere

  • Studieleder: 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.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

31. mars 2026

Primær fullføring (Antatt)

30. september 2028

Studiet fullført (Antatt)

30. september 2029

Datoer for studieregistrering

Først innsendt

1. mai 2026

Først innsendt som oppfylte QC-kriteriene

10. mai 2026

Først lagt ut (Faktiske)

15. mai 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

15. mai 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

10. mai 2026

Sist bekreftet

1. mai 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • C202505161

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

IPD-planbeskrivelse

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

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

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