How Should You Treat Muscle Mass Loss in GLP-1 Patients?

With glucagon-like peptide 1 (GLP-1) agonists now close to inducing weight loss at levels only seen before through surgical intervention, obesity specialists say patients on these drugs are experiencing complications similar to those seen after weight loss surgery.

One such unintended outcome? Muscle mass loss.

“Muscle mass loss in these patients is very common,” said Caissa Troutman, MD, an obesity medicine specialist and founder of WEIGHT reMDy, a direct care wellness practice in Camp Hill, Pennsylvania.

Studies suggest muscle loss with GLP-1 receptor agonists (GLP-1 RAs) ranges from fat-free mass (FFM) decreases of 25%-39% of the total weight lost over 36-72 weeks. The substantial muscle loss is largely attributed to the magnitude of weight loss, rather than an independent effect of GLP-1 RAs, according to a 2024 analysis in The Lancet Diabetes & Endocrinology.

By comparison, non-pharmacological caloric restriction with smaller magnitudes of weight loss results in 10%-30% FFM losses, The Lancet study found. In addition, the decline in muscle mass with GLP-1 RAs is several times greater than that expected from age-related muscle loss (0.8% per year based on 8% muscle loss per decade from ages 40 to 70 years).

“Dismissing the importance of muscle loss can create a disconnect between patients’ increased awareness of muscle and the role it plays in health,” lead study author Carla Prado, PhD, RD, wrote in the study.

Key Approaches to Prevent, Mitigate Muscle Loss

Troutman says two approaches are key to addressing muscle mass loss in patients losing weight with GLP-1 medications: Increased protein intake and physical activity.

The recommended dietary allowance (RDA) for protein is 0.8 g/kg for most adults, while the acceptable macronutrient distribution range is 10%-35% of total energy, Troutman noted. For reference, a diet of 0.8 g/kg translates to roughly 70 g of protein for a 200-lb person. A 4-oz chicken breast has about 35 g of protein.

Research shows that consuming more protein than recommended offers an FFM or skeletal muscle preservation benefit.

A 2024 analysis of studies in the Journal of the Endocrine Society, for example, illustrates that consuming twice the RDA of protein during a 40% energy deficit reduces FFM loss. In addition, protein intakes of 1.1-1.6 g/kg preserved FFM during weight loss better than protein intakes of between 0.6 and 0.9 g/kg in patients with obesity.

Troutman recommends practical nutrition strategies to help patients increase their protein intake such as targeting 20-40 g of protein each time a person eats, which is consistent with maximum stimulation of muscle protein synthesis. Patients can also aim to consume protein three or more separate times each day and/or plan each meal around a high-quality protein source.

Anila Chadha, MD, recommends that patients on GLP-1 agonists aim for 30 g of protein at every meal and emphasize both protein and vegetables. Strategic dosing is also important to avoid rapid weight loss, said Chadha, a family physician and obesity medicine physician at Dignity Health in Bakersfield, California.

Rapid weight loss can lead to sarcopenia, a progressive form of muscle loss that causes muscle weakness, she said. Sarcopenia is often associated with older age, but research shows obesity-associated sarcopenia can happen in patients in weight management settings.

To prevent rapid weight loss, Chadha refrains from incrementing patients’ doses of GLP-1 analogs every 4 weeks, she said. Instead, she increases the dose when patients start to plateau on the same dose or their food cravings come back.

“This prevents rapid weight loss and rapid muscle loss,” she said.

The Obesity Medicine Association does not have a clinical practice statement or guidelines specific to protein/dietary recommendations for patients on GLP-1 agonists. A 2022 analysis in Obesity Pillars, the association’s journal, concluded that further research is needed to understand the unique nutritional needs of adults on GLP-1 or dual glucose-dependent insulinotropic polypeptide/GLP-1 RAs and to support the development of individual nutritional guidelines.

Implementing the Right Movement Plan

In addition to a high-protein diet, obesity specialist Catherine Varney, DO, incorporates strengthening exercises early for her patients on GLP-1 medications.

The higher a patient’s body mass index, the more likely they are to injure themselves with weight-bearing cardiovascular exercise. But resistance training, even in a sitting position, is an exercise they can do early in their program, said Varney, an assistant professor and obesity medicine director for the University of Virginia Health, Charlottesville, Virginia.

The Journal of the Endocrine Society analysis found that exercise helps prevent FFM loss during weight loss, particularly resistance training. The activity prevents the typical reductions in daily myofibrillar protein synthesis and the postabsorptive muscle protein synthesis typically observed with energy restriction, according to the study.

“Many studies have shown that exercise contributes very little to weight loss, but it’s very important for cardiovascular health, mental health, weight maintenance, and preventing excess muscle mass loss with weight loss,” Varney said. “So, when looking at the risk/benefit of exercise, we sometimes hold off on cardiovascular exercise in the beginning but always stress the importance of strengthening training.”

Troutman said physicians should encourage patients to engage in 150 min/wk of moderate-intensity aerobic (endurance) activity and an appropriately designed resistance training program. If clinicians have access to a bioelectrical impedance scale, they can also track skeletal muscle mass and address any significant drop in lean muscle mass, she added.

“What I typically see is that patients who do well with keeping their protein up and engage in strength training, they see maintenance of muscle mass,” she said. “I have had some patients lose moderate amounts due to poor eating habits, which we try to course correct.”

All weight loss inevitably results in some muscle mass loss, Varney emphasized. That’s why it’s critical that physicians include counseling on nutritious, nonrestrictive dietary changes and a movement plan for these patients.

“My biggest fear with these medications is that they are not being prescribed along with a comprehensive plan, which puts them at greater risk of weight loss complications,” she said. “All weight loss is not good, especially if there is excess muscle mass loss, which can lead to a host of other problems including malnutrition, sarcopenia, and falls with injury.”

If physicians don’t feel comfortable, don’t have the time, or are still learning more about these interventions, Varney recommended they identify resources in the community to refer the patient to a registered dietician, physical therapist, or exercise facility for guidance.