Glucagon-like Peptide 1 (GLP-1) Receptor Agonist Therapy and Exercise Training in People With Obesity
- Conditions
- ObesitySkeletal Muscle
- Interventions
- Behavioral: Exercise training
- Registration Number
- NCT07091500
- Lead Sponsor
- Washington University School of Medicine
- 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, and muscle strength in response to GLP-1 RA therapy, with or without exercise training, and subsequent treatment cessation on muscle-related outcomes.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 40
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description GLP-1 RA Semaglutide Participants in this group will receive semaglutide therapy along with diet behavior counseling for 52 weeks GLP-1 RA + Exercise Exercise training Participants in this group will receive semaglutide therapy along with diet behavior counseling and exercise training for 52 weeks. GLP-1 RA + Exercise Semaglutide Participants in this group will receive semaglutide therapy along with diet behavior counseling and exercise training for 52 weeks.
- Primary Outcome Measures
Name Time Method Body composition Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention DEXA scan
Physical function Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention Score on the Modified Physical Performance Test
- Secondary Outcome Measures
Name Time Method Insulin sensitivity Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention Whole-body insulin sensitivity during a hyperinsulinemic-euglycemic clamp
Muscular Strength for the Seated Row exercise Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention Upper body muscle strength will be assessed as a ten repetition maximal strength for the seated row exercise
Muscular Strength for the Leg Flexion exercise Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention Lower body muscle strength will be assessed as a ten repetition maximal strength for the leg flexion exercise
Muscle mass Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention Whole-body muscle mass will assessed by using the D3-creatine dilution method
Muscle volume Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention Magnetic resonance scans
Muscular Strength for the Chest Press exercise Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention 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
Muscular Strength for the Leg Press exercise Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention Lower body muscle strength will be assessed as a ten repetition maximal strength for the leg press exercise