Semaglutide plus exercise training for people with obesity and reduced physical function

Effect of GLP-1 Receptor Agonist Therapy With and Without Exercise Training on Muscle Mass and Physical Function in People With Obesity

This two-year trial will test whether semaglutide, with or without a supervised exercise program, helps people with obesity and decreased physical function keep muscle mass, strength, and metabolic health and what happens after the medication is stopped.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 50 Years to 75 Years
• Sex: All
• Sponsor: Washington University School of Medicine (Academic / other)
• Locations: 1 site (St Louis, Missouri)
• Trial ID: NCT07091500 on ClinicalTrials.gov

What this trial studies

This is a two-year randomized clinical trial at Washington University School of Medicine that assigns adults with obesity and reduced physical function to semaglutide with or without a structured exercise training program. Investigators will measure body composition, skeletal muscle physical and metabolic function, and muscle strength during treatment and after a planned treatment cessation period. Key eligibility criteria include BMI ≥ 30 and a Modified Physical Performance Test score of 17–31, with exclusions for diabetes, significant cardiopulmonary disease, prior GLP‑1 therapy, or high baseline exercise levels. The design aims to define both the immediate effects of GLP‑1 receptor agonist therapy combined with exercise and the longer-term consequences when therapy is stopped.

Who should consider this trial

Good fit: Adults with obesity (BMI ≥30 kg/m2), decreased physical function (Modified Physical Performance Test 17–31), and approval from their primary physician are the intended participants.

Not a fit: People with diabetes, significant cardiopulmonary or other major organ dysfunction, current GLP‑1 or other weight‑loss medication use, very high baseline exercise (>150 min/week), or recent unstable weight are excluded and may not benefit from or be eligible for this protocol.

Why it matters

Potential benefit: If successful, this approach could help people with obesity preserve skeletal muscle mass, strength, and metabolic function during weight loss and reduce decline after stopping GLP‑1 therapy.

How similar studies have performed: GLP‑1 receptor agonists like semaglutide have repeatedly produced substantial weight loss and metabolic improvements in prior trials, but their effects on skeletal muscle mass and function, combined with exercise, and the impact of stopping therapy are largely unstudied.

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

Where this trial is running

St Louis, Missouri

• Washington University School of Medicine — St Louis, Missouri, United States (Recruiting)

Study contacts

• Principal investigator: Samuel Klein, MD — Washington University School of Medicine
• Study coordinator: Coordinator

Conditions Obesity; Skeletal Muscle