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

Combatting Muscle Loss in Obese Adult Patients on GLP-1 Medications Through Dietary Counseling and Exercise During Treatment

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Muscle Loss; Obesity & Overweight; Dietary Assessment; GLP - 1; Exercise Intervention
• Intervention / Treatment: Drug: Semaglutide; Behavioral: Dietary Counseling; Behavioral: Exercise

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Anatolia Vick-Kregel; Phone Number: 17135157991; Email: av82@rice.edu
• Study Contact Backup: Name: Brad Lambert; Email: bslambert@houstonmethodist.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77005
      • Rice University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Arm: GLP-1 Therapy Alone; Participants receive standard-of-care GLP-1 receptor agonist therapy (semaglutide) without additional exercise or dietary counseling.	Drug: Semaglutide; FDA-approved GLP-1 receptor agonist administered once weekly per standard of care; Other Names: Wegovy®
Experimental: Treatment Arm: GLP-1 Therapy + Exercise and Dietary Counseling; 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; Weekly individualized nutrition counseling focused on nutrition education, meal planning, and macronutrient intake to support lean mass preservation during GLP-1 therapy.; Behavioral: Exercise; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Skeletal Muscle Mass	Change in skeletal muscle mass measured by dual-energy X-ray absorptiometry (DEXA).	Baseline to 12 weeks

Collaborators and Investigators

• Sponsor: William Marsh Rice University
• Collaborators: The Methodist Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (Estimated): April 6, 2026
• Primary Completion (Estimated): June 29, 2026
• Study Completion (Estimated): August 6, 2026

Study Registration Dates

• First Submitted: April 21, 2026
• First Submitted That Met QC Criteria: April 21, 2026
• First Posted (Actual): April 28, 2026

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: GLP-1; obesity; Semaglutide; exercise intervention
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neuromuscular Manifestations; Nutrition Disorders; Pathological Conditions, Anatomical; Overnutrition; Body Weight; Atrophy; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Muscular Atrophy; Health Care Quality, Access, and Evaluation; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Investigative Techniques; Epidemiologic Methods; Data Collection; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Epidemiologic Measurements; Exercise; semaglutide; Nutrition Assessment
• Other Study ID Numbers: IRB-FY2026-226

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data will be shared. Shared IPD will include demographic characteristics (e.g., age, sex), baseline and post-intervention outcome measures related to body composition, muscle mass, bone mineral density, muscular strength, cardiorespiratory fitness, dietary intake summaries, and selected laboratory values. All shared data will be stripped of direct identifiers and coded to prevent re-identification. No names, dates of birth, contact information, medical record numbers, or other direct personal identifiers will be shared.
• IPD Sharing Time Frame: Not sure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No