Muscle Loss on GLP-1 Medications: The Known and the Unknown

When weight comes off quickly, some of it is not fat. That is true of almost every kind of weight loss, and it has become a big question for people using GLP-1 medications. Here is what the two best-known body-composition studies found, and the good news they hold, because the picture is more reassuring than the headlines suggest.

First, what “lean mass” means

Body-composition scans, usually a type called DXA, split the body into fat, bone and everything else. That “everything else” is called lean mass. It includes muscle, but also water, organs and connective tissue. So a drop in lean mass on a scan is not the same thing as a drop in muscle, and it is not the same as losing strength. The researchers behind one of the studies below make the same point: scans are useful, but they are an estimate.

What the trials measured

The semaglutide figures come from an exploratory analysis presented as a conference abstract and reported in the medical press, so treat them as early. The tirzepatide figures come from a peer-reviewed paper by Look and colleagues in Diabetes, Obesity and Metabolism in 2025.

Is that a lot? Here is the reassuring part

This is the part people often miss. In the tirzepatide study, the placebo group also lost about a quarter of its weight loss as lean mass. The authors concluded that the split, roughly three parts fat to one part lean, was consistent with other ways of losing weight. In other words, the medication did not appear to cause unusually large lean-mass loss compared with weight loss in general. The study also notes that people on tirzepatide reported better physical function, even though their scans showed less lean mass. That is encouraging news for you.

What we do not know yet

• What happens to muscle strength over time. The trials were built to measure weight, not to track strength, so they cannot answer this well.
• Older adults and people who are already frail. Losing lean mass matters more when you start with little to spare, and the sub-studies were small.
• What happens after the medication stops. Our guide to what happens when you stop a GLP-1 medication covers regain, but how lean mass changes afterward is less clear.
• Whether specific habits protect muscle on these medications. We did not find trial evidence in the sources we reviewed that shows exactly how much strength training or extra protein changes the picture for people on GLP-1 treatment.

Friendly things you can do

None of this is a reason to change treatment on your own. These are general ideas to talk through with your prescriber or a registered dietitian:

• Ask about it. If you have a history of low muscle mass, falls or limited mobility, bring it up early.
• Look at protein. Our guide to how much protein you actually need explains the current guideline range. Your own needs depend on your health, so check with a professional, especially if you have kidney disease.
• Use your muscles. Regular strength work is recommended for adults in general. Our guide to strength training for beginners starts from the U.S. activity guidelines.
• Look at function, not just the scale. Can you climb stairs, carry shopping and get up from a chair easily? Those everyday wins may say more than a number.

Where this leaves you

Some lean mass is lost whenever weight is lost, and the best trial data on GLP-1 treatment suggest the proportion is similar to other approaches. The open questions are about long-term strength and older adults, and the research is still catching up. If you are using or considering one of these medications, ask your clinician how to keep an eye on muscle along the way. For background on how these medications work, see our explainer on why researchers are so interested in GLP-1 medications.

Sources

1. Look M, Dunn JP, Kushner RF, et al. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight. Diabetes, Obesity and Metabolism, 2025. PMC11965027
2. Wilding J. Semaglutide 2.4 mg body composition (STEP 1 DXA sub-study), presented at ENDO 2021 and reported by Patient Care Online. Patient Care Online