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.
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.
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])
Parallel
Exercise training
BehavioralParticipants will perform supervised exercise training sessions 3 days per week and unsupervised at-home sessions 2-3 days per week.
Semaglutide
Drugsemaglutide 2.4 mg subcutaneous per week or max tolerated dose and diet behavior counseling
Therapy Cessation
BehavioralAfter 1 year of treatment, participants will stop taking GLP-1 medications (and exercise, if applicable)
Physical function
Score on the Modified Physical Performance Test
Body composition
DEXA scan
Muscle mass
Whole-body muscle mass will assessed by using the D3-creatine dilution method
Muscle volume
Magnetic resonance scans
Insulin sensitivity
Whole-body insulin sensitivity during a hyperinsulinemic-euglycemic clamp
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
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