Do GLP-1 Medications Cause Muscle Loss? Understanding Lean Body Mass During Weight Loss

Table of Contents

Medically reviewed and updated for 2026
Dr. Richard Lipman MD
Board Certified Internal Medicine /Endocrinologist

Much of the concern about “muscle loss” with GLP-1 medications stems from a misunderstanding of what a DEXA scan actually measures. A decrease in lean body mass is often reported and interpreted as skeletal muscle loss, but lean body mass includes far more than skeletal muscle. Headlines warning of “major muscle loss” with medications such as Zepbound® and Mounjaro®, and newer oral GLP-1 therapies, frequently oversimplify the science. The reality is far more nuanced.

Lean Body Mass Loss vs. Muscle Loss

The whole-body DEXA scan, as shown in Figure 1 below, indicates that some lean body mass is lost when people lose weight, but lean body mass includes more than just muscle. It also covers water, glycogen, connective tissue, organs, and other non-fat parts of the body.

Weight Loss Involves Continuous Changing Metabolic Adaptations

In the early weeks of treatment, much of the so-called “lean mass” loss is actually due to the loss of glycogen and the water that comes with it, not muscle breakdown. As weight loss continues, most of the loss comes from body fat.

By eating enough protein, doing regular resistance exercise, and losing weight gradually, most people can keep most of their muscle while losing a significant amount of fat.

Figure 1: Whole Body DEXA Scanner
Dual-energy X-ray absorptiometry (DEXA) scan, often called a “Whole-Body” DEXA scan, is highly valued in fitness and sports medicine for accurately assessing body composition (body fat percentage, lean muscle mass, and visceral fat). It is a quick, painless, low-dose X-ray.

A vivid, color-coded illustration depicting three human figures in a standing position against a black background. Each figure shows a unique distribution of body fat and muscle, rendered in striking hues of red, blue, and yellow, highlighting anatomical structures and variations in physique.

Figure 2: DEXA scan; orange areas are fat deposits

1. What is lean body mass?

Lean body mass (LBM) is everything in your body except fat. It includes muscle, organs, bones, connective tissue, and water. To find your LBM, subtract your fat mass from your total body weight.

2. Is lean body mass the same as muscle?

No. Skeletal muscle is only one part of LBM, along with organs, bones, and body water. This means that changes in LBM do not always reflect changes in muscle alone,

3. Why DEXA scans can be misleading.

DEXA scans group muscle, organs, connective tissue, and water together into a single “lean mass” number. Because of this, DEXA scans cannot distinguish between actual muscle loss and changes in organs and body fluids. Factors such as hydration, recent food intake, and the time of day can affect the results, so short-term comparisons are not always reliable.

4. What happens during the first month? (glycogen and water)

In the beginning, most of the quick weight loss comes from water and glycogen, not fat or muscle. Each gram of stored glycogen holds about three grams of water. Eating fewer carbs and less food in the first month can make both your weight and “lean mass” drop more than you might expect.

5. What happens after 5%, 10%, 15%, and 20% weight loss?

As people lose more weight, they also lose more lean mass, but the ratio of fat to lean mass lost usually stays about the same. When someone loses 15 to 20% of their body weight, which often happens with tirzepatide or semaglutide, it is normal to lose several kilograms of lean mass. Wilding reported in the STEP 1 trial: LBM loss of 9.7% with fat loss of 19%. In adults with overweight/obesity, semaglutide 2.4 mg was associated with reduced total fat mass and regional visceral fat mass, and an increased proportion of lean body mass. Greater weight loss was associated with greater improvement in body composition (lean body mass:fat mass ratio).

Figure 3 shows the loss of lean body mass broken down into components:

A detailed table highlighting the components of lean body mass lost during weight loss. The background is a soft blue, and each category is neatly arranged in cells. Key components are in bold red font, including 'Skeletal Muscle,' with values indicating their share of weight loss. The table includes clear headings and concise percentages, enhancing readability and structure.

Note the loss of muscle mass: 10-15%, not the 40% reported in several older studies. That is why it is important to keep focusing on preserving muscle throughout weight loss, not just at the start.

6. Semaglutide vs. tirzepatide vs. oral GLP-1s.

Research shows that semaglutide can lead to a loss of up to 40% of total weight, including lean mass. In the STEP-1 trial, about 40% of the weight lost was lean mass, while tirzepatide in the SURMOUNT-1 DNA SUBSTUDY trial showed a 25% decrease in LBM.

Some studies report tirzepatide’s number as close to 34%. In real-world settings, tirzepatide sometimes leads to greater lean mass loss than semaglutide over time, so it is unclear which one better protects muscle mass. Oral GLP-1s usually cause less total weight loss, so there is less lean mass loss overall, but the percentage lost as lean tissue is about the same.

The best way to keep muscle is to eat 1.2 to 1.6 grams of protein per kilogram of body weight each day, do resistance training two or three times a week, and avoid cutting calories too much. Since appetite suppression can make it harder to get enough protein, try to include protein in every meal. Studies show that resistance training and adequate protein intake can largely prevent lean mass loss. Getfitcraft

8. Common myths about GLP-1 and muscle loss.

Myth: GLP-1s directly cause muscle “wasting” like a disease. In reality, clinical data show these drugs do not directly cause muscle wasting. Changes in lean mass are a normal part of weight loss and reduced calorie intake, as with any major weight-loss method.

Myth: All the “lean mass” lost is muscle. In fact, much of it is water, glycogen, and other tissues.

Summary of Metabolic Changes During Weight Loss

Figure 2 below was created from data from several studies, including the Surmont studies, and it attempts to put the whole weight loss process together, including % body weight loss, what is actually lost with examples, and ending with muscle loss. Here is a summary of the current information.

GLP-1 medications do not appear to directly cause muscle breakdown.
Most forms of weight loss typically result in some reduction of lean mass.
Early reductions in “lean mass” observed on DEXA scans are attributable to water and glycogen loss rather than permanent muscle loss.
Most individuals lose significantly more fat than muscle, particularly when consuming adequate protein and engaging in resistance training.
Current research indicates that tirzepatide may preserve lean mass more effectively than semaglutide.
Research on newer oral medications such as orforglipron is ongoing, so it is too early to determine their effectiveness in preserving muscle mass
Figure 2: Metabolic Changes During Weight Loss: The Muscle Loss Issue

A detailed infographic illustrating muscle loss related to weight loss percentages, featuring colorful icons of fat, glycogen, and water droplets. Each section contrasts muscle loss risks and tissue types in a grid layout, providing clear visual distinctions and educational insights.

Why Losing Some Lean Body Mass During Weight Loss Is Normal—and Often Healthy

Patients hear “40% lean mass loss” and assume they are losing 40% of their muscle. In reality, the changes include alterations in:

Lean body mass includes water
glycogen
organs
connective tissue
blood
skeletal muscle