GLP-1 Medications and Muscle Loss: What to Know About Nutrition and Supplements

Medications such as semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) are changing how obesity and metabolic disease are treated. Many people taking these medications are seeing substantial weight loss, often faster than expected.

What’s less often discussed is that the number on the scale doesn’t tell the full story. Along with fat loss, some people also lose lean body mass, which includes muscle, water and other tissues. In some studies, lean mass has accounted for a meaningful portion of total weight lost.

GLP-1 stands for glucagon-like peptide-1, a hormone naturally produced in the gut. It plays an important role in regulating appetite and blood sugar.

GLP-1 receptor agonists, which are the class of medications that includes semaglutide and tirzepatide, work by mimicking this hormone. Their effects include:

• Increasing feelings of fullness after eating
• Slowing the rate at which the stomach empties
• Reducing appetite and food intake
• Supporting blood sugar control

These medications were originally developed to treat type 2 diabetes. They are now widely used for weight management and have also been shown to reduce cardiovascular risk in certain populations.

In clinical trials, people taking these medications often lose 15% to 20% of their body weight, which is greater than what was typically seen with earlier weight-loss medications.

Beyond weight loss, GLP-1 therapies have been associated with improvements in:

• Blood sugar control
• Cardiovascular outcomes
• Fatty liver disease
• Obesity-related conditions such as sleep apnea and joint pain

These are meaningful benefits. At the same time, rapid weight loss, regardless of method, introduces important considerations for muscle and nutritional health.

Weight loss is not made up of fat alone. When people lose weight quickly, they typically lose a combination of fat mass and lean body mass.

How much muscle is lost?

Research suggests that approximately 25% to 40% of weight loss during GLP-1 therapy may come from lean mass. This can sound concerning, but it’s important to understand what that means.

Lean mass is not just muscle

Lean body mass includes:

• Skeletal muscle
• Organs
• Bone
• Body water
• Connective tissue

This means that not all lean mass loss reflects a loss of muscle. Some of the change may be related to shifts in fluid balance or other tissues.

Is this unique to GLP-1 medications?

No. This pattern is not unique to GLP-1 therapy. Any form of significant weight loss, including calorie restriction or bariatric surgery, typically results in some degree of lean mass loss.

In some cases, changes in muscle during weight loss may also reflect improvements in muscle quality, including reduced fat infiltration and improved metabolic function.

Why muscle still matters

Even when expected, muscle loss deserves attention.

Skeletal muscle is:

• A major contributor to resting metabolic rate
• A key site for glucose metabolism
• Essential for strength, mobility and independence

Losing muscle can lower the number of calories your body burns at rest. This may make it easier to regain weight if treatment is stopped, especially since many people discontinue GLP-1 medications within the first year.

Who is most at risk?

Certain groups may be more vulnerable to the effects of muscle loss:

• Older adults
• Individuals with low baseline muscle mass
• People who are physically inactive
• Women in perimenopause or postmenopause

In these populations, muscle loss can contribute to sarcopenia (age-related muscle decline) and increase the risk of falls, frailty and reduced independence.

Protein supplements

Protein supplements can help fill gaps when food intake is limited.

• Whey protein is well studied and effective for supporting muscle
• Plant-based options such as pea protein can also be effective

However, protein alone is not enough.

Exercise, particularly strength training, is one of the most important factors in preserving muscle during weight loss.

Why resistance training matters

Resistance training:

• Stimulates muscle protein synthesis
• Helps maintain or increase muscle mass
• Improves strength and physical function

Studies consistently show that people who combine GLP-1 therapy with structured exercise are more likely to preserve lean mass than those who do not.

What about aerobic exercise?

Aerobic activity is important for cardiovascular health, but it is less effective than resistance training for preserving muscle.

A balanced approach that includes both is ideal.

Getting started

If you’re new to exercise:

• Begin with bodyweight movements (such as squats or wall push-ups)
• Use resistance bands or light weights
• Focus on consistency rather than intensity
• Gradually increase difficulty over time

Even small amounts of strength training can make a meaningful difference.

Reduced food intake can increase the risk of vitamin and mineral deficiencies.

Some studies suggest that a notable portion of people taking GLP-1 medications develop at least one nutritional deficiency within the first year.

Common nutrients of concern

Vitamin D

• Important for bone, muscle and immune health
• Deficiency is common, especially in people with obesity

Calcium

• Essential for bone strength
• Blood levels may appear normal even when intake is low

Vitamin B12

• Supports nerve function and energy metabolism
• Low levels may cause fatigue, numbness or cognitive changes

Magnesium

• Involved in muscle function and energy production
• Often under-consumed in general diets

Iron

• Important for oxygen transport in the blood
• Risk may be higher in menstruating women

Signs of possible deficiency

• Fatigue
• Muscle weakness
• Hair loss
• Slow wound healing
• Unusual bruising

Should you take a multivitamin?

A daily multivitamin may help address general gaps in intake. However, targeted supplementation based on lab testing is often more effective.

Talk with your health care professional about appropriate testing and supplementation.

Common side effects of GLP-1 medications include:

• Nausea
• Vomiting
• Constipation
• Diarrhea

These symptoms can affect more than comfort; they can also reduce food intake and worsen nutritional deficiencies.

Practical strategies

• Eat smaller meals
• Eat slowly and mindfully
• Avoid high-fat or heavily processed foods
• Stay well hydrated
• Speak with your health care professional before adjusting your dose

Managing these symptoms can improve both adherence and overall nutrition.

If you are taking or considering a GLP-1 medication, consider discussing:

• Baseline lab testing (vitamin D, B12, iron, calcium, magnesium)
• Follow-up testing within 3 to 6 months
• Referral to a registered dietitian
• A personalized exercise plan that includes strength training
• Bone density evaluation if appropriate
• Ongoing monitoring of dietary intake and hydration

Proactive care can help identify and address potential issues early.

Researchers are exploring ways to improve body composition outcomes during GLP-1 therapy.

Early studies suggest that combining GLP-1 medications with other therapies may:

• Increase fat loss
• Reduce muscle loss

These approaches are still under investigation and are not yet widely available. However, they reflect a broader shift toward focusing not just on weight loss, but on overall body composition and health.

GLP-1 medications represent a significant advance in the treatment of obesity and metabolic disease. For many people, they offer meaningful improvements in health and quality of life.

Muscle loss during weight loss is a real consideration, but it is not unique to these medications, and it can be addressed.

The most effective approach includes:

• Adequate protein intake
• Regular resistance training
• Monitoring of key nutrients
• Ongoing communication with a health care professional

These strategies can help you preserve muscle, support long-term health and maintain the benefits of treatment.

Before starting any supplement or making significant changes to your routine, talk with your health care professional to determine what’s right for you.

Sources: 

Does ozempic cause muscle loss and how to prevent it?. Drugs.com. (n.d.). https://www.drugs.com/medical-answers/ozempic-cause-muscle-loss-how-you-prevent-3578660 

ExerciseContributor, A. C. on, Author American Council on Exercise Contributor Read More Less, GreenContributor, D. J., GrahamContributor, K., & Expert, P. M. and F. (n.d.). CertifiedTM: June 2025 - GLP-1s and Lean Mass: What the research shows. ACE. https://www.acefitness.org/continuing-education/certified/june-2025/8892/glp-1s-and-lean-mass-what-the-research-shows/ 

ScienceDaily. (2025, February 24). Genetic evidence that diabetes drug GLP-1 receptor agonists achieve weight loss primarily by reducing fat mass more than muscle. ScienceDaily. https://www.sciencedaily.com/releases/2025/02/250224111937.htm 

TNF Pharmaceuticals Launches Study Series aimed at preserving lean muscle mass during GLP-1 Weight Loss treatment | American Pharmaceutical Review - the review of American Pharmaceutical Business & Technology. (n.d.-f). https://www.americanpharmaceuticalreview.com/1315-News/617450-TNF-Pharmaceuticals-Launches-Study-Series-Aimed-at-Preserving-Lean-Muscle-Mass-During-GLP-1-Weight-Loss-Treatment/