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

Launched by WASHINGTON UNIVERSITY SCHOOL OF MEDICINE · Jul 21, 2025

Keywords

ClinConnect Summary

This clinical trial is studying how a type of medication called GLP-1 receptor agonists, often used to help with weight loss, affects muscle health and physical function in people with obesity. The study will look at whether combining this medication with exercise improves muscle strength and metabolism better than the medication alone. It will also explore what happens to muscle health when people stop taking the medication, since many stop within a year and may regain weight.

To take part, individuals need to have obesity (a body mass index of 30 or higher), lower than normal muscle mass, some difficulty with physical activities, and signs of insulin resistance (a condition related to how the body handles sugar). Participants must get their doctor’s approval and meet other health criteria. The study will last two years, and participants may receive the medication with or without an exercise program. This research is important because it could help people with obesity keep their muscle strength and stay healthier during and after weight loss treatment.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • i) obesity (Body Mass Index ≥ 30 kg/m2)
• • ii) low muscle mass \[percent total body weight as appendicular lean mass (ALM/ body weight) of \<19.4% for women and \<25.7% for men 8\])
• • iii) decreased physical function (Modified Physical Performance Test score 17 to 31)
• • iv) insulin resistance (defined as Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) score \>2.5)
• • v) 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) calcitonin level of ≥20 ng/L if eGFR ≥60 mL/min/1.73 m2 or ≥35 ng/L if eGFR \<60 mL/min/1.73 m2
• • xii) family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
• • xiii) 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
• • xiv) 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
• • xv) 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
• • xvi) have had bariatric surgery or plan to have endoscopic or bariatric surgery therapy for obesity
• • xvii) anemia (Hgb \<10 g/dL)
• • xviii) 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)
• • xix) history of seizure disorder
• • xx) Female who is pregnant, breast-feeding or intends to become pregnant
• • xxi) allergy or hypersensitivity to GLP-1 RA medications
• • xxii) unable to grant voluntary informed consent
• • xxiii) 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