Semaglutide and Tirzepatide for Genetic Aging Delay in Adults With Obesity

Second Affiliated Hospital, Zhejiang University, School of Medicine66 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Adults With Simple Obesity

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: Baseline and Week 24