Semaglutide and Tirzepatide for Genetic Aging Delay in Adults With Obesity

Zhejiang University

Status: Enrolling

Conditions: Adults With Simple Obesity

Treatments: Drug: Semaglutide; Drug: Tirzepatide; Drug: Metformin

Study type: Interventional

Funder types: Other

Identifiers

NCT07293325

2025-0568

Details and patient eligibility

About

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.

Enrollment: 66 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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66 participants in 3 patient groups

Semaglutide Group

Experimental group

Description:

Semaglutide administered once weekly by subcutaneous iniection. Dose titrated from 0.25 mg to 2.0 mg as tolerated over 24 weeks

Treatment:

Drug: Semaglutide

Tirzepatide Group

Experimental group

Description:

Tirzepatide administered once weekly by subcutaneous injection. Dose titrated from 2.5 mg to 10 mg as tolerated over 24 weeks

Treatment:

Drug: Tirzepatide

Metformin Group

Active Comparator group

Description:

Metformin administered orally. Dose titrated from 500 mg to 1500-2000 mg daily, based on tolerance, for 24 weeks.

Treatment:

Drug: Metformin