Semaglutide, Tirzepatide, or Metformin to slow biological age 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 24-week test gives semaglutide, tirzepatide, or metformin to adults with obesity to see if the drugs slow or reverse accelerated biological (epigenetic) aging.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 66 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (Academic / other)
• Locations: 1 site (Hangzhou)
• Trial ID: NCT07293325 on ClinicalTrials.gov

What this trial studies

This is a prospective, randomized, open-label trial enrolling 66 adults with simple obesity who have not used weight-loss medications in the prior 3 months. Participants are randomized to receive semaglutide, tirzepatide, or metformin for 24 weeks with regular clinical visits and measurements. The primary biological outcome is change in DNA methylation age measured by the iWatchAge test, while the study also tracks inflammatory markers, metabolic parameters, and body composition. The goal is to determine whether incretin-based therapies produce measurable changes in epigenetic aging markers alongside metabolic improvements.

Who should consider this trial

Good fit: Adults aged 18–75 with simple obesity (BMI ≥ 30 kg/m²) who have not used anti-obesity medications in the past 3 months and who can attend study visits and provide informed consent are the ideal candidates.

Not a fit: People with secondary causes of obesity, diabetes requiring glucose-lowering drugs, recent bariatric surgery, severe heart/liver/kidney/psychiatric disease, or pregnant or breastfeeding women are unlikely to be eligible or benefit from this protocol.

Why it matters

Potential benefit: If successful, these treatments could slow or partially reverse obesity-related accelerated epigenetic aging and improve metabolic and inflammatory biomarkers that link obesity to long-term disease risk.

How similar studies have performed: GLP-1 receptor agonists and tirzepatide have strong evidence for weight loss and metabolic benefit, but direct evidence that these drugs reverse DNA methylation (epigenetic) age is limited and largely novel.

Eligibility criteria

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.

Where this trial is running

Hangzhou

• The Second Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou, China (Recruiting)

Study contacts

• Study coordinator: Chao Zheng

Conditions Adults With Simple Obesity