ObesityNCT07091500
Glucagon-like Peptide 1 (GLP-1) Receptor Agonist Therapy and Exercise Training in People With Obesity
A study testing Exercise training, Semaglutide and Therapy Cessation in people with Obesity and Skeletal Muscle, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 75 years
- Conditions the study is for
- Obesity, Skeletal Muscle, Brain Connectivity
- What is being tested?
- Exercise training, Semaglutide and Therapy Cessation
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Aug 2025to 1 Aug 2029
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Coordinator, 314-273-1879
About this study
Official title: Effect of GLP-1 Receptor Agonist Therapy With and Without Exercise Training on Muscle Mass and Physical Function in People With Obesity
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
- Being tested
- Exercise training, Semaglutide, Therapy Cessation
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exercise trainingBehavioural
Participants will perform supervised exercise training sessions 3 days per week and unsupervised at-home sessions 2-3 days per week.
SemaglutideDrug
semaglutide 2.4 mg subcutaneous per week or max tolerated dose and diet behavior counseling
Therapy CessationBehavioural
After 1 year of treatment, participants will stop taking GLP-1 medications (and exercise, if applicable)
| Study group | Role | What they receive |
|---|---|---|
| GLP-1 RA | Active comparator | Participants in this group will receive semaglutide therapy along with diet behavior counseling for 52 weeks Receives: Drug: Semaglutide; Behavioral: Therapy Cessation |
| GLP-1 RA + Exercise | Experimental | Participants in this group will receive semaglutide therapy along with diet behavior counseling and exercise training for 52 weeks. Receives: Behavioral: Exercise training; Drug: Semaglutide; Behavioral: Therapy Cessation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Physical function
Score on the Modified Physical Performance Test
Measured: Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention
Body composition
DEXA scan
Measured: Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention
Secondary outcomes (8)
Muscle mass
Whole-body muscle mass will assessed by using the D3-creatine dilution method
Measured: Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention
Muscle volume
Magnetic resonance scans
Measured: Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention
Insulin sensitivity
Whole-body insulin sensitivity during a hyperinsulinemic-euglycemic clamp
Measured: Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention
Muscular Strength for the Chest Press exercise
Upper body muscle strength will be assessed as a ten repetition maximal strength for the chest press exercise on a Hoist multi-station weight machine
Measured: Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention
Muscular Strength for the Seated Row exercise
Upper body muscle strength will be assessed as a ten repetition maximal strength for the seated row exercise
Measured: Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention
Muscular Strength for the Leg Press exercise
Lower body muscle strength will be assessed as a ten repetition maximal strength for the leg press exercise
Measured: Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention
Muscular Strength for the Leg Flexion exercise
Lower body muscle strength will be assessed as a ten repetition maximal strength for the leg flexion exercise
Measured: Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention
Neural Connectivity
GLP-1 receptor-agonist-induced neural connectivity as determined by functional magnetic resonance imaging (fMRI) scanning
Measured: Before (baseline), at the end of dose escalation (around weeks 18-20), at the end of maximal treatment (around 52 weeks), and after treatment cessation (anytime after 60 weeks) in a subset of participants randomized to the semaglutide only group.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2025
- Study start11 Aug 2025
- Primary completion1 Aug 2028 (estimated)
- Study completion1 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joseph W Beals, PhD, Study director, Washington University School of MedicineSamuel Klein, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07091500
- Sponsor's protocol ID
- 202505162
- Status last verified
- Jul 2026
- First submitted
- 10 Jul 2025
- Last updated
- 10 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No