The GLP-1 RA and dual GIP/GLP-1 RA medications are everywhere right now. These medications have reshaped conversations around weight, metabolism, and chronic disease. But alongside their rise, a key question has emerged:
What’s happening to muscle mass during weight loss on GLP-1 receptor agonists (GLP-1 RAs)?
The answer is nuanced—and clinically important.
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As a refresher: glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) are two gut derived incretin hormones that play roles in glucose and insulin metabolism. GLP-1 Receptor Agonists (GLP-RA) are a class of medications that mimic the hormone glucagon-like peptide 1 (GLP-1), helping to regulate insulin release, glucose metabolism, and appetite. Dual GIP/GLP-1 receptor agonists are medications that target both GIP and GLP-1 receptors. Either GLP-1 RA alone or the dual agonists are being used to assist with appetite regulation, satiety, improved insulin release, and weight management.
For a refresher on the GLP-1 and GIP hormones, check out on our blog on GLP-1 and GIP hormones: What do they do?
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In thinking about GLP-1 medications and lean mass, the first myth we need to clarify is:
Weight Loss ≠ Just Fat/Adipose Tissue Loss
Any time the body loses weight, it loses a combination of:
- Adipose/fat mass
- Lean mass (including skeletal muscle)
Research on GLP-1 RAs suggests that while a significant portion of weight loss comes from fat, a meaningful percentage can also come from lean mass (upwards of 40%).
This isn’t unique to these medications, it’s true of most weight loss interventions. However, the mechanisms of GLP-1 RAs introduce some specific considerations.
Why Muscle Loss Can Occur with GLP-1 Medications
1. Reduced Energy Intake
GLP-1 RAs work largely in part by decreasing appetite and increasing satiety. While this can support reduced energy intake, it can also lead to:
- Inadequate total energy intake
- Insufficient protein consumption
Both are key drivers of muscle loss.
2. Rapid Weight Loss
Faster rates of weight loss are associated with greater losses of lean mass. This is a protective mechanism the body employs as a form of self-preservation; sparing muscle to preserve adipose or fat tissue, which cushions, warms, and protects the organs. Fat is also more energy dense, meaning we get more energy from it, making it more desirable for the body to hold on to! Some individuals on GLP-1 RAs experience rapid changes, particularly early in treatment.
For context, the Academy of Nutrition and Dietetics defines greater than 5% body weight loss in 1 month as not only significant, but one of the clinical markers of malnutrition due to the effects of rapid weight loss on lean mass and overall metabolism.
3. Inadequate Resistance Stimulus
Muscle is metabolically active tissue that requires stimulus to be maintained. Without adequate resistance training, the body has less reason to preserve muscle during periods of weight loss.
Why Muscle Matters
Skeletal muscle is not just about strength or aesthetics, it plays a central role in:
- Glucose metabolism
- Insulin sensitivity
- Functional capacity and longevity
- Resting energy expenditure
Loss of muscle mass can:
- Reduce metabolic rate over time
- Impact physical function
- Increase risk for weight regain
Is This “Muscle Loss” Always Harmful?
Not necessarily.
For individuals with higher baseline adiposity, some loss of lean mass during weight reduction is expected and not inherently harmful, particularly if:
- Overall metabolic health is improving
- Physical function is maintained
- Adequate energy intake is prioritized
However, the concern increases when:
- Protein and overall energy intake is low
- Physical activity (especially resistance training) is minimal
- Weight loss is aggressive and fast
- There is a history of underfueling and/or eating disorders
A Critical Consideration: Eating Disorders & Underfueling
For individuals with a history of restrictive eating, the risk profile changes.
Appetite suppression + reduced intake can:
- Reinforce underfueling
- Increase risk of disproportionate lean mass loss
- Further disconnect individuals from internal hunger cues
In these cases, muscle loss is not just a physiological concern, it’s part of a broader pattern of inadequate nourishment.
How to Support Muscle While on GLP-1 RAs
If GLP-1 RAs are being used, protecting lean mass should be part of the plan:
1. Prioritize Protein (as part of adequate overall energy)
Adequate protein intake supports muscle protein synthesis. Needs vary, but many individuals benefit from:
- Distributing protein across meals
- Including protein even when appetite is low
BUT! It’s not just about protein! Overall energy intake is important here. If the body is not getting adequate amounts of other macronutrients, amino acids from protein will be shifted to making glucose rather than for muscle purposes.
2. Incorporate Resistance Training
Strength training provides the stimulus needed to maintain (or even build) muscle during weight loss.
3. Avoid Excessive Restriction
More is not always better when it comes to calorie reduction. Undereating accelerates muscle loss and undermines long-term outcomes, particularly in terms of metabolism and bone density.
Additionally, more research is emerging on the nutrient deficiencies associated with use of these medications, in instances where energy intake is insufficient.
4. Monitor More Than Weight
Focusing solely on the scale can be misleading. Consider:
- Strength and function
- Energy levels
- Body composition analysis
- Biochemical data/nutrient status
The Bottom Line
Muscle loss during weight loss is not new, but it deserves more attention in the context of GLP-1 RAs, especially given their effects on appetite and intake.
Continue the Conversation
We recently sat down with Pete Kupprion of Koop Strength on our podcast, Eat Kale and Cupcakes, to discuss how he approaches training in clients using GLP-1 medications.
Through adequate nutrition and training support, hear us talk about our mutual client who has minimized the amount of muscle lost, while prioritizing loss of adipose tissue.
Listen to the podcast Episode with Pete here: Episode 4: Interview with Pete Kupprion – GLP-1s, Body Composition, and Smarter Movement as We Age
Also hear Laura and Shannon discuss GLP-1s and what we are considering as dietitians on Episode 3.
Lastly, if you or someone you know is considering or using GLP-1 medications, check out our GLP-1 Masterclass. Get it here
This master class is perfect for anyone on or considering GLP-1/GIP medications who wants to feel confident, nourished, and supported on their journey.
References:
McCarthy D, Berg A. Weight Loss Strategies and the Risk of Skeletal Muscle Mass Loss. Nutrients. 2021;13(7):2473. Published 2021 Jul 20. doi:10.3390/nu13072473
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. doi:10.1111/dom.15728
Scott Butsch W, Sulo S, Chang AT, et al. Nutritional deficiencies and muscle loss in adults with type 2 diabetes using GLP-1 receptor agonists: A retrospective observational study. Obes Pillars. 2025;15:100186. Published 2025 Jun 10. doi:10.1016/j.obpill.2025.100186
White JV, Guenter P, Jensen G, et al. Consensus statement: Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition). JPEN J Parenter Enteral Nutr. 2012;36(3):275-283. doi:10.1177/0148607112440285
