Recruiting

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

Sponsor:

Washington University School of Medicine

Code:

NCT07091500

Conditions

Obesity

Skeletal Muscle

Brain Connectivity

Eligibility Criteria

Sex: All

Age: 50 - 70+

Healthy Volunteers: Not accepted

Interventions

Exercise training

Semaglutide

Therapy Cessation

Study Details

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, muscle strength and appetite control and reward signaling in the brain in response to 1-year of GLP-1 RA therapy, with or without exercise training, and subsequent treatment cessation on muscle and appetite-related outcomes assessed 1-year after stopping treatment.

Conditions

Obesity

Skeletal Muscle

Brain Connectivity

Study ID

NCT07091500

Start date

Aug 11, 2025

Status verified date

Jul, 2026

Completion date

Aug 1, 2029

Anticipated

Primary completion date

Aug 1, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 50 - 70+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

40 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

active comparator: GLP-1 RA

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

experimental: GLP-1 RA + Exercise

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

Interventions

Exercise training

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

Semaglutide

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

Therapy Cessation

After 1 year of treatment, participants will stop taking GLP-1 medications (and exercise, if applicable)

Primary outcome measure

Physical function [ Time Frame: Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention ]
Body composition [ Time Frame: Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention ]

Central Contacts and Locations

Central contacts

Coordinator

314-273-1879 NutritionResearch@wustl.edu

Locations

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Coordinator

314-273-1879

More Information

Sponsor

Washington University School of Medicine

Last update posted

Jul 10, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Washington University School of Medicine on 2026-07-10.