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This study is a prospective, randomized, open-label clinical trial enrolling 66 adults with simple obesity who have not used weight-loss medications for at least 3 months. Participants will receive semaglutide, tirzepatide, or metformin for 24 weeks. Changes in "biological (epigenetic) age" will be assessed using the iWatchAge DNA methylation age test, while simultaneously monitoring improvements in aging-related biomarkers such as inflammatory factors, metabolic parameters, and body composition. The aim is to determine whether incretin-based therapies can reverse or slow obesity-related accelerated epigenetic aging and to provide new clinical evidence for interventions targeting obesity and aging.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Semaglutide Group | Experimental | Semaglutide administered once weekly by subcutaneous iniection. Dose titrated from 0.25 mg to 2.0 mg as tolerated over 24 weeks |
|
| Tirzepatide Group | Experimental | Tirzepatide administered once weekly by subcutaneous injection. Dose titrated from 2.5 mg to 10 mg as tolerated over 24 weeks |
|
| Metformin Group | Active Comparator | Metformin administered orally. Dose titrated from 500 mg to 1500-2000 mg daily, based on tolerance, for 24 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Semaglutide | Drug | Semaglutide administered once weekly by subcutaneous injection.Dose titrated from 0.25 mg to 2.0 mg as tolerated over 24 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in DNA methylation-based biological age measured by iWatchAge | Change in epigenetic biological age from baseline to Week 24, measured using the iWatchAge DNA methylation assay. This outcome reflects whether semaglutide, tirzepatide, or metformin can delay or reverse obesity-associated accelerated epigenetic aging. | Baseline and Week 24 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Chao Zheng | Contact | 18857116176 | chao_zheng@zju.edu.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Second Affiliated Hospital, Zhejiang University School of Medicine | Recruiting | Hangzhou | China |
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| ID | Term |
|---|---|
| C000591245 | semaglutide |
| D000098860 | Tirzepatide |
| D008687 | Metformin |
| ID | Term |
|---|---|
| D000067757 | Glucagon-Like Peptide-1 Receptor |
| D000067756 | Glucagon-Like Peptide Receptors |
| D043562 | Receptors, G-Protein-Coupled |
| D011956 | Receptors, Cell Surface |
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| Tirzepatide | Drug | Tirzepatide administered once weekly by subcutaneous injection. Dose titrated from 2.5 mg to 10 mg as tolerated over 24 weeks |
|
| Metformin | Drug | Metformin administered orally. Dose titrated from 500 mg to 1500-2000 mg daily, based on tolerance, for 24 weeks |
|
| D008565 | Membrane Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011964 | Receptors, Gastrointestinal Hormone |
| D018000 | Receptors, Peptide |
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |