Combatting Muscle Loss in Obese Adult Patients on GLP-1 Medications Through Dietary Counseling and Exercise During Treatment Evaluates Whether a 12-week Exercise and Individualized Nutrition Program Can Reduce Muscle and Bone Loss and Improve Strength, Fitness, and Function in Obese Adults on GLP-1

NCT07554417 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: IRB-FY2026-226
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity remains a critical public health challenge and is associated with increased rates of morbidity, mortality, and chronic disease worldwide. In recent years, glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, have emerged as highly effective pharmacological treatments for obesity, producing substantial weight loss and favorable metabolic improvements. These medications are now widely prescribed, with estimates suggesting that nearly 12% of Americans are currently using or have previously used GLP-1 therapies. Despite their demonstrated benefits, growing evidence indicates that GLP-1-associated weight loss may be accompanied by unintended reductions in skeletal muscle and bone mass. This potential side effect is of increasing concern, as muscle and bone are essential for metabolic health, physical function, injury prevention, and recovery from illness or surgical intervention. Loss of skeletal muscle during weight reduction may negatively impact strength, mobility, insulin sensitivity, and long-term health outcomes. These risks may be further compounded in individuals experiencing reduced physical activity, mechanical unloading, or prolonged caloric deficits. In clinical and surgical populations, such as individuals undergoing orthopedic procedures, mechanical unloading and disuse already predispose patients to muscle and bone atrophy. When combined with pharmacologically induced weight loss, these factors may further hinder recovery, impair functional capacity, and compromise musculoskeletal integrity. As GLP-1 therapies are increasingly adopted across diverse populations, understanding how to preserve lean mass and bone health during treatment has become an important clinical and public health priority. Exercise training, particularly resistance training, combined with appropriate nutritional support, has consistently been shown to preserve and enhance skeletal muscle and bone mass during weight loss. Structured exercise interventions can mitigate sarcopenia and osteopenia while improving muscular strength, cardiorespiratory fitness, metabolic health, and overall physical function. Similarly, individualized dietary counseling, particularly when focused on adequate protein intake and nutrient timing, plays a critical role in supporting muscle protein synthesis and skeletal health during caloric restriction. Together, these lifestyle strategies may not only counteract the potential adverse musculoskeletal effects associated with GLP-1 therapy but also enhance treatment efficacy by improving cardiovascular risk profiles, insulin sensitivity, systemic inflammation, and physical resilience. Despite the growing use of GLP-1 medications, there remains a limited body of prospective research examining structured lifestyle interventions specifically designed to preserve muscle and bone mass during GLP-1-induced weight loss. Addressing this gap is essential to ensure that pharmacological obesity treatments support long-term health, functional independence, and quality of life. Integrating exercise and nutrition interventions into GLP-1 treatment protocols may represent a scalable and clinically meaningful strategy to optimize outcomes and reduce unintended consequences of rapid weight loss. The purpose of this study is to evaluate whether a structured lifestyle intervention combining exercise and individualized nutritional counseling can mitigate skeletal muscle mass loss in obese adults undergoing treatment with GLP-1 receptor agonists. The primary objective of this study is to determine whether participation in a structured 12-week exercise program, in conjunction with individualized dietary counseling, preserves skeletal muscle mass and bone mineral density during GLP-1 therapy. Secondary objectives include assessing changes in muscular strength, cardiorespiratory fitness, and overall functional capacity. Findings from this study aim to inform best practices for integrating lifestyle interventions with pharmacological obesity treatments and to support safer, more effective, and functionally protective approaches to weight management in adults receiving GLP-1 therapy.

Conditions

Muscle Loss; Exercise Intervention; Dietary Assessment; GLP - 1; Obesity & Overweight

Keywords

GLP-1; Semaglutide; obesity; exercise intervention

Outcome Measures

Primary Outcomes (1)

• Change in Skeletal Muscle Mass

  Change in skeletal muscle mass measured by dual-energy X-ray absorptiometry (DEXA).

  Baseline to 12 weeks

Study Arms (2)

Control Arm: GLP-1 Therapy Alone

ACTIVE COMPARATOR

Participants receive standard-of-care GLP-1 receptor agonist therapy (semaglutide) without additional exercise or dietary counseling.

Drug: Semaglutide

Treatment Arm: GLP-1 Therapy + Exercise and Dietary Counseling

EXPERIMENTAL

Participants receive standard-of-care GLP-1 receptor agonist therapy (semaglutide) in combination with a 12-week structured exercise program and weekly individualized dietary counseling.

Behavioral: Dietary Counseling; Behavioral: Exercise

Interventions

Semaglutide DRUG

FDA-approved GLP-1 receptor agonist administered once weekly per standard of care

Also known as: Wegovy®

Control Arm: GLP-1 Therapy Alone

Dietary Counseling BEHAVIORAL

Weekly individualized nutrition counseling focused on nutrition education, meal planning, and macronutrient intake to support lean mass preservation during GLP-1 therapy.

Treatment Arm: GLP-1 Therapy + Exercise and Dietary Counseling

Exercise BEHAVIORAL

A 12-week supervised and progressive exercise program consisting of resistance training and aerobic exercise performed three times per week at the Rice University Wellness Center.

Treatment Arm: GLP-1 Therapy + Exercise and Dietary Counseling

Eligibility Criteria

• Age: 40 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 40 and 55 years
• Body Mass Index (BMI) greater than 30
• Body fat percentage greater than 30% for males and 40% for females
• Android to gynoid fat ratio greater than 1.0
• Currently eligible for GLP-1 therapy
• No diagnosis of Type II diabetes

You may not qualify if:

• Presence of abnormal ECG findings, including arrhythmias or ischemic changes
• Hypertensive response to exercise, defined as systolic blood pressure exceeding 250 mmHg or diastolic pressure exceeding 115 mmHg
• Hypotensive response to exercise, defined as a drop in systolic pressure greater than 10 mmHg with increasing workload
• VO₂ max below 15 ml/kg/min
• Borg Rating of Perceived Exertion (RPE) greater than 19 during submaximal workloads
• Any contraindications to exercise as defined by ACSM guidelines
• Musculoskeletal limitations that prevent safe participation in exercise

Sponsors & Collaborators

• William Marsh Rice University: lead
• The Methodist Hospital Research Institute: collaborator

Study Sites (1)

Rice University

Houston, Texas, 77005, United States

Location

MeSH Terms

Conditions

Obesity; Overweight; Muscular Atrophy

Interventions

semaglutide; Nutrition Assessment; Exercise

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Epidemiologic Measurements; Public Health; Environment and Public Health; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Central Study Contacts

Anatolia Vick-Kregel

CONTACT

17135157991; av82@rice.edu

Brad Lambert

CONTACT

bslambert@houstonmethodist.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study uses a parallel-group design in which participants are randomized to either standard-of-care GLP-1 therapy alone or GLP-1 therapy combined with structured exercise and dietary counseling for 12 weeks.

Study Record Dates

• First Submitted: April 21, 2026
• First Posted: April 28, 2026
• Study Start: April 6, 2026
• Primary Completion (Estimated): June 29, 2026
• Study Completion (Estimated): August 6, 2026
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Not sure.

Locations

US (1)