Semaglutide and Tirzepatide for Genetic Aging Delay in Adults With Obesity

Assessing the Role of GLP-1 Receptor Agonist Semaglutide and Dual GLP-I/GIP Receptor Agonist Tirzepatide in Delaying Genetic Aging in Adult Obese Patients Using the iWatchAge Technology

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.

Study Overview

• Status: Recruiting
• Conditions: Adults With Simple Obesity
• Intervention / Treatment: Drug: Semaglutide; Drug: Tirzepatide; Drug: Metformin

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chao Zheng; Phone Number: 18857116176; Email: chao_zheng@zju.edu.cn

Study Locations

• China
  • Hangzhou, China
    • Recruiting
    • The Second Affiliated Hospital, Zhejiang University School of Medicine
    • Contact: Chao Zheng; Phone Number: 18857116176; Email: chao_zheng@zju.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Adults aged 18 to 75 years.
2. Diagnosed with simple obesity, defined as BMI ≥ 30 kg/m².
3. Have not used any anti-obesity medications (including GLP-1 RAs, tirzepatide, metformin for weight loss, etc.) within the past 3 months.
4. Able and willing to comply with study procedures and complete follow-up assessments.
5. Provide written informed consent.

Exclusion Criteria:

1. Presence of secondary obesity (e.g., endocrine disorders such as Cushing's syndrome or hypothyroidism).
2. Use of anti-obesity medications or participation in another weight-loss program within the past 3 months.
3. Diagnosed type 1 or type 2 diabetes mellitus requiring hypoglycemic drug therapy.
4. History of pancreatitis, severe gastrointestinal disease, or bariatric surgery.
5. Severe cardiovascular, hepatic, renal, or psychiatric disease that may affect participation.
6. Pregnant or breastfeeding women, or women planning pregnancy during the study period.
7. Current participation in any other clinical trial.
8. Any condition that, in the investigator's judgment, makes the participant unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide Group; Semaglutide administered once weekly by subcutaneous iniection. Dose titrated from 0.25 mg to 2.0 mg as tolerated over 24 weeks	Drug: Semaglutide; Semaglutide administered once weekly by subcutaneous injection.Dose titrated from 0.25 mg to 2.0 mg as tolerated over 24 weeks
Experimental: Tirzepatide Group; Tirzepatide administered once weekly by subcutaneous injection. Dose titrated from 2.5 mg to 10 mg as tolerated over 24 weeks	Drug: Tirzepatide; Tirzepatide administered once weekly by subcutaneous injection. Dose titrated from 2.5 mg to 10 mg as tolerated over 24 weeks
Active Comparator: Metformin Group; Metformin administered orally. Dose titrated from 500 mg to 1500-2000 mg daily, based on tolerance, for 24 weeks.	Drug: Metformin; Metformin administered orally. Dose titrated from 500 mg to 1500-2000 mg daily, based on tolerance, for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2025
• Primary Completion (Estimated): April 2, 2027
• Study Completion (Estimated): June 2, 2027

Study Registration Dates

• First Submitted: November 24, 2025
• First Submitted That Met QC Criteria: December 18, 2025
• First Posted (Actual): December 19, 2025

Study Record Updates

• Last Update Posted (Actual): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 18, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Biguanides; Guanidines; Amidines; Metformin; Tirzepatide; semaglutide
• Other Study ID Numbers: 2025-0568

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No