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

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• 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
• Email: NutritionResearch@wustl.edu
• Phone: 314-273-1879

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.