GLP-1 receptor agonist medications—including Ozempic®, Wegovy®, Mounjaro®, and Zepbound®—are now commonly used in the management of obesity and type 2 diabetes. These medications can produce meaningful improvements in weight and metabolic health. As their use becomes more widespread, clinicians and patients alike are paying closer attention to how GLP-1 therapy may affect muscle mass, mobility, and physical function.
Physical activity and rehabilitation are not new concepts in weight management, but the rapid body composition changes associated with GLP-1 medications create specific considerations for movement and musculoskeletal health.
What Are GLP-1 Medications?
GLP-1 receptor agonists work by mimicking glucagon-like peptide-1, a hormone involved in appetite regulation and glucose control. By increasing satiety, slowing gastric emptying, and improving insulin response, these medications help reduce caloric intake and improve blood sugar regulation.
Weight loss achieved with GLP-1 therapy, however, is not limited to fat tissue. Research suggests that approximately 15–40% of total weight lost may come from fat-free mass, including skeletal muscle, with variability depending on age, baseline health, and activity levels [1–3]. This has important implications for physical function, especially during periods of rapid weight loss.
Why Muscle Loss Matters
Skeletal muscle supports far more than strength. It plays a central role in joint stability, balance, glucose metabolism, and daily functional tasks such as walking, lifting, and climbing stairs. Loss of lean muscle mass can contribute to:
- Reduced strength and endurance
- Increased joint discomfort
- Declines in balance and mobility
- Greater risk of injury or falls
- Impaired metabolic health
For individuals with osteoarthritis, diabetes, cardiovascular disease, or low baseline activity levels, muscle loss may have a meaningful impact on symptoms and long-term health.
Physical Therapy Considerations During GLP-1 Therapy
Physical therapy focuses on restoring and maintaining movement quality, strength, and functional capacity. When individuals are taking GLP-1 medications, rehabilitation strategies often emphasize thoughtful progression rather than rapid increases in activity.
Supporting Muscle Strength
Resistance training is widely recognized as an effective strategy for preserving muscle mass during weight loss [1–4]. Physical therapists can help tailor strength programs to individual needs, accounting for joint health, prior injuries, and current tolerance to loading.
Managing Changes in Activity Tolerance
As weight decreases, many people find movement easier and increase their activity levels. While this is often positive, sudden changes in workload can stress muscles and tendons that are not yet conditioned. Gradual progression allows tissues time to adapt.
Joint and Bone Health
Weight loss reduces mechanical load across joints, which may relieve pain but also reduces skeletal loading. Weight-bearing and strengthening exercises help maintain bone health and joint resilience during this transition [4].
Preparing for Long-Term Function
Many individuals discontinue GLP-1 therapy over time. Establishing sustainable movement habits during treatment may help support long-term weight maintenance and functional independence once medication is reduced or stopped [4].
Who May Benefit Most From a Structured Exercise Approach?
Individuals who may benefit from structured rehabilitation or guided exercise during GLP-1 therapy include those with:
- Obesity or type 2 diabetes
- Chronic joint pain or osteoarthritis
- Reduced mobility or deconditioning
- Elevated risk of sarcopenia
- Obesity-related heart failure with preserved ejection fraction (HFpEF)
In these groups, exercise and rehabilitation support muscle preservation, functional capacity, and injury prevention alongside pharmacologic treatment [2,5,6].
A Broader Perspective on Care
GLP-1 medications represent one component of a broader health picture. Their effectiveness is influenced by movement habits, nutrition, mental health, and access to care. Physical therapy often complements medical and nutritional management by addressing how the body adapts to weight loss and increased activity.
Current evidence suggests that GLP-1 medications do not diminish the benefits of exercise or rehabilitation. Instead, their impact on body composition highlights the importance of maintaining muscle health and functional movement [4].
Summary
GLP-1 receptor agonists have changed the landscape of obesity and diabetes management. While these medications can be effective tools, changes in muscle mass and physical function deserve careful attention. Maintaining strength, mobility, and joint health through appropriate exercise and rehabilitation is an important consideration for supporting long-term health during and after GLP-1 therapy.
References
- Chavez AM, Carrasco Barria R, León-Sanz M. Nutrition Support Whilst on Glucagon-Like Peptide-1 Based Therapy. Is It Necessary? Curr Opin Clin Nutr Metab Care. 2025;28(4):351–357.
- Neeland IJ, Linge J, Birkenfeld AL. Changes in Lean Body Mass With Glucagon-Like Peptide-1-Based Therapies and Mitigation Strategies. Diabetes Obes Metab. 2024;26(Suppl 4):16–27.
- Ceasovschih A, Asaftei A, Lupo MG, et al. Glucagon-Like Peptide-1 Receptor Agonists and Muscle Mass Effects. Pharmacol Res. 2025;220:107927.
- Mulcahy J, DeLaRosby A, Norwood T. Transforming Care: Implications of Glucagon-Like Peptide-1 Receptor Agonists on Physical Therapist Practice. Phys Ther. 2025;105(6):pzaf061.
- Cannata A, McDonagh TA. Heart Failure With Preserved Ejection Fraction. N Engl J Med. 2025;392(2):173–184.
- Monzo L, Savarese G, Mullens W, et al. Pharmacological Treatment for Patients With Obesity and Heart Failure: Focus on GLP-1 Receptor Agonists. Eur J Heart Fail. 2025.