Changes in Body Composition Including Muscle With Anti-Obesity Medications, Both With and Without Exercise

Changes in Body Composition Including Muscle With Anti-Obesity Medications, Both With and Without Exercise

The goal of this clinical trial is to learn whether adding either cardiovascular exercise or resistance exercise to pharmacotherapy treatment for obesity improves the retention of lean mass compared to pharmacotherapy alone in adults with overweight or obesity who are prescribed pharmacotherapy for obesity treatment by their personal physician. It will also provide information about whether either form of exercise added to pharmacotherapy for obesity treatment has additional benefits on other health and fitness measurements. The main questions it aims to answer are:

• Is there a difference in the change in total lean body mass between pharmacotherapy alone and either pharmacotherapy plus cardiovascular exercise or pharmacotherapy plus resistance exercise?
• Is there a difference in the change in muscle mass between the intervention conditions (pharmacotherapy alone, pharmacotherapy plus cardiovascular exercise, pharmacotherapy plus resistance exercise)?
• Is there a difference in the change in muscle quality between the intervention conditions (pharmacotherapy alone, pharmacotherapy plus cardiovascular exercise, pharmacotherapy plus resistance exercise)?
• Is there a difference in the change in body weight between the intervention conditions (pharmacotherapy alone, pharmacotherapy plus cardiovascular exercise, pharmacotherapy plus resistance exercise)?
• Is there a difference in the change in body composition (fat mass, fat mass distribution) between the intervention conditions (pharmacotherapy alone, pharmacotherapy plus cardiovascular exercise, pharmacotherapy plus resistance exercise)?
• Is there a difference in the change in cardiorespiratory fitness between the intervention conditions (pharmacotherapy alone, pharmacotherapy plus cardiovascular exercise, pharmacotherapy plus resistance exercise)?
• Is there a difference in the change in muscle strength between the intervention conditions (pharmacotherapy alone, pharmacotherapy plus cardiovascular exercise, pharmacotherapy plus resistance exercise)?
• Is there a difference in the change in physical function between the intervention conditions (pharmacotherapy alone, pharmacotherapy plus cardiovascular exercise, pharmacotherapy plus resistance exercise)?
• Is there a difference in the change in bone mineral density between the intervention conditions (pharmacotherapy alone, pharmacotherapy plus cardiovascular exercise, pharmacotherapy plus resistance exercise)?
• Is there a difference in the change in bone biomarkers between the intervention conditions (pharmacotherapy alone, pharmacotherapy plus cardiovascular exercise, pharmacotherapy plus resistance exercise)?
• Is there a difference in the change in resting blood pressure between the intervention conditions (pharmacotherapy alone, pharmacotherapy plus cardiovascular exercise, pharmacotherapy plus resistance exercise)?
• Is there a difference in the change in energy intake between the intervention conditions (pharmacotherapy alone, pharmacotherapy plus cardiovascular exercise, pharmacotherapy plus resistance exercise)?
• Is there a difference in the change in physical activity between the intervention conditions (pharmacotherapy alone, pharmacotherapy plus cardiovascular exercise, pharmacotherapy plus resistance exercise)?
• Is there an effect of sex, race/ethnicity, age, menopausal status, obesity management medication type, or other demographic characteristics on the outcomes that are being measured.
• What is the extent to which the retention of lean body mass or muscle mass mediates the effect of exercise on weight changes.

Participants will:

• Initiate and continue throughout the study period an eligible obesity management medication that is prescribed by their healthcare provider, and to report their adherence to this medication to the investigators.
• Participant in this study for a period of 6-8 months to complete outcome assessments that occur at baseline and at the conclusion of 6 months of the intervention period, and monitoring visits that occur at weeks 3, 6, 9, 12, 15, 18, and 21.
• If attend 3 supervised exercise sessions per week if assigned to either the cardiovascular exercise intervention or the resistance training intervention for a period of 24 weeks.

Inclusion Criteria:

• Both males and females of all race/ethnic groups are eligible for participation in this study.
• 18 to <65 years of age.
• Newly prescribed FDA-approved obesity manage medication that can include Tirzepatide, Semaglutide, or up to 4 additional next-generation obesity management medications (will receive DSMB approval prior to inclusion), approval for treatment (pharmacy, insurance, etc.), and the participant agreeing to start this treatment and continue treatment for at least 6 months (the participant will be recruited prior to this medication being initiated).
• Body mass index (BMI) of >=27.0 kg/m2 with at least one weight-related complication (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease) provided it does not compromise the ability to safely complete the screening or outcome measures or to engage in the prescribed exercise interventions), or >=30 kg/m2 without weight-related complications. We will not limit enrollment based on an upper BMI level provided that the participant meets the other eligibility requirements. However, the participant will be excluded if they exceed the weight or size limits of the dual-energy x-ray absorptiometry (DXA) system that is used to assess body composition or the MRI that is used to assess muscle quality.
• Ability to provide informed consent prior to participation in this study.
• Clearance from the study physician for meeting all eligibility criteria for this study.

Exclusion Criteria:

• Type 2 diabetes.
• Report moderate-to-vigorous exercise for >60 min/week, and >1 day/week of structured cardiovascular or resistance exercise over the past 3 months.
• Report sustained weight loss of >=3% in the past 3 months.
• History of metabolic/bariatric surgery.
• Females who are pregnant or breastfeeding or reporting a planned pregnancy during the study period.
• Report a current medical condition or treatment for a medical condition that could affect body weight or contradict engagement in any aspect of the outcome measures or interventions.
• History of muscle conditions that may impact the quality of muscle or response to the study interventions (e.g., myopathy, muscular dystrophy, rhabdomyolysis, etc.).
• Contraindications to MRI (e.g., metal implants that are not MRI safe, etc.). NOTE: Participants who are otherwise eligible other than being contraindicated for the MRI scan will be eligible and the MRI scan will not be performed as a research procedure.
• Current congestive heart failure, angina, uncontrolled arrhythmia, symptoms indicative of an increased acute risk for a cardiovascular event, prior myocardial infarction or history of cardiomyopathy, coronary artery bypass grafting or angioplasty, conditions requiring chronic anticoagulation (i.e., recent or recurrent DVT).
• Resting systolic blood pressure of >=160 mmHg or resting diastolic blood pressure of >=100 mmHg. If medicated for blood pressure control, the medication dose needs to be stable for >=6 months.
• Eating disorders that would contraindicate weight loss or physical activity.
• Alcohol or substance abuse.
• Current psychological condition that is untreated, hospitalization for a psychological condition within the past 12 months, or not being on a stable dose of treatment for at least 6 months.
• Report plans to relocate to a location not accessible to the study site or having employment, personal, or travel commitments that prohibit attendance at scheduled intervention sessions or assessments.