Glucagon-like Peptide 1 (GLP-1) Receptor Agonist Therapy and Exercise Training in People With Obesity

NCT ID: NCT07091500

Last Updated: 2025-09-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-11
• Study Completion Date: 2029-08-01

Brief Summary

The use of glucagon-like peptide receptor agonists (GLP-1 RAs) may have clinically important effects on skeletal muscle mass (SMM), and physical function. The effects of exercise training in conjunction with GLP-1 RA therapy on these outcomes has not been studied. Additionally, most people treated with GLP-1-based weight loss medications stop taking these medications within 1 year of initiating treatment. This is an important clinical concern because weight regain can occur after weight loss pharmacotherapy is stopped and the impact of stopping GLP-1 RA therapy on physical and metabolic function has not been studied.

In this study, the investigators will conduct a 2-year randomized clinical trial to evaluate body composition, muscle physical and metabolic function, and muscle strength in response to GLP-1 RA therapy, with or without exercise training, and subsequent treatment cessation on muscle-related outcomes.

Conditions

Obesity; Skeletal Muscle

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

GLP-1 RA

Participants in this group will receive semaglutide therapy along with diet behavior counseling for 52 weeks

Group Type: ACTIVE_COMPARATOR

Semaglutide

Intervention Type: DRUG

semaglutide 2.4 mg subcutaneous per week or max tolerated dose and diet behavior counseling

GLP-1 RA + Exercise

Participants in this group will receive semaglutide therapy along with diet behavior counseling and exercise training for 52 weeks.

Group Type: EXPERIMENTAL

Exercise training

Intervention Type: BEHAVIORAL

Participants will perform supervised exercise training sessions 3 days per week and unsupervised at-home sessions 2-3 days per week.

Semaglutide

Intervention Type: DRUG

semaglutide 2.4 mg subcutaneous per week or max tolerated dose and diet behavior counseling

Interventions

Exercise training

Participants will perform supervised exercise training sessions 3 days per week and unsupervised at-home sessions 2-3 days per week.

Intervention Type: BEHAVIORAL

Semaglutide

semaglutide 2.4 mg subcutaneous per week or max tolerated dose and diet behavior counseling

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• i) obesity (Body Mass Index ≥ 30 kg/m2)
• ii) decreased physical function (Modified Physical Performance Test score 17 to 31)
• iii) approval of their primary physician to participate in this study.

Exclusion Criteria

• i) unstable weight (>4% change during the last 2 months before entering the study)
• ii) ≥150 min per week of structured exercise (e.g., jogging, activities that cause heavy breathing and sweating)
• iii) diabetes
• iv) significant cardiopulmonary disease (heart failure, angina, uncontrolled hypertension, chronic obstructive pulmonary disease) or other organ dysfunction (e.g., renal insufficiency [eGFR <30 mL/min/1.73 m2])
• v) therapy with a GLP-1 or other weight loss medications
• vi) clinically significant gastric emptying abnormality or chronically take drugs that directly affect gastrointestinal motility
• vii) history of chronic or acute pancreatitis
• viii) thyroid-stimulating hormone (TSH) >1.5X the upper limit of normal (patients receiving treatment for hypothyroidism may be included provided their thyroid hormone replacement dose has been stable for at least 3 months)
• ix) history of significantly active or unstable Major Depressive Disorder or other severe psychiatric disorder (e.g. schizophrenia, bipolar disorder, or other serious mood or anxiety disorder) within the last 2 months that would interfere with study participation
• x) acute or chronic hepatitis, or other liver disease other than Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD)
• xi) family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
• xii) history of active or untreated malignancy or are in remission from a clinically significant malignancy (other than basal- or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years
• xiii) tobacco use, excessive alcohol intake (≥3 drinks/day for men and ≥2 drinks/day for women) or active substance abuse with illegal drugs by self-report, or regular marijuana use within 3 months of enrollment and unwilling to abstain from marijuana during the trial
• xiv) Use of medications that are known to affect the study outcome measures or increase the risk of study procedures and that cannot be temporarily discontinued for this study
• xv) have had bariatric surgery or plan to have endoscopic or bariatric surgery therapy for obesity
• xvi) anemia (Hgb <10 g/dL)
• xvii) Conditions that render subject unable to complete all testing procedures (e.g., severe ambulatory impairments, limb amputations, or metal implants that interfere with imaging procedures; coagulation disorders)
• xii) history of seizure disorder
• xix) Female who is pregnant, breast-feeding or intends to become pregnant
• xx) allergy or hypersensitivity to GLP-1 RA medications
• xxi) unable to grant voluntary informed consent
• xxii) unable or unwilling to follow the study protocol or who, for any reason, the research team considers the participant is not an appropriate candidate for the study

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph W Beals, PhD

Role: STUDY_DIRECTOR

Washington University School of Medicine

Samuel Klein, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Coordinator

Role: CONTACT

NutritionResearch@wustl.edu

314-273-1879

Facility Contacts

Coordinator

Role: primary

314-273-1879

Other Identifiers

202505162

Identifier Type: -

Identifier Source: org_study_id