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

NCT07091500 | Recruiting DMC

• 1 other identifier: 202505162
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• Physical function

  Score on the Modified Physical Performance Test

  Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention

• Body composition

  DEXA scan

  Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention

Secondary Outcomes (7)

• Muscle mass

  Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention

• Muscle volume

  Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention

• Insulin sensitivity

  Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention

• Muscular Strength for the Chest Press exercise

  Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention

• Muscular Strength for the Seated Row exercise

  Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention

Study Arms (2)

GLP-1 RA

ACTIVE COMPARATOR

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

Drug: Semaglutide

GLP-1 RA + Exercise

EXPERIMENTAL

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

Behavioral: Exercise training; Drug: Semaglutide

Interventions

Exercise training BEHAVIORAL

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

GLP-1 RA + Exercise

Semaglutide DRUG

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

GLP-1 RA; GLP-1 RA + Exercise

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

MeSH Terms

Conditions

Obesity

Interventions

Exercise; semaglutide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Joseph W Beals, PhD

  Washington University School of Medicine

  STUDY DIRECTOR

• Samuel Klein, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Coordinator

CONTACT

314-273-1879; NutritionResearch@wustl.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2025
• First Posted: July 29, 2025
• Study Start: August 11, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2029
• Last Updated: September 23, 2025

Record last verified: 2025-09

Locations

US (1)