By Dr. Asnat Raziel, specialist in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal
Lean body mass: weight loss is not only fat
Lean body mass is one of the most discussed topics in obesity drug treatment. The new drugs, including semaglutide, liraglutide and tirzepatide, allow major weight loss and better metabolic markers. However, the more effective treatments become, the more an important question arises: what exactly are we losing? Is it mainly fat, or does muscle also suffer?
A systematic review and meta-analysis published in June 2026 in the International Journal of Obesity looked at this question. It included seven randomized controlled trials with 821 patients with obesity. All patients received GLP-1 drugs at obesity treatment doses, compared with placebo.
What is lean body mass, and why is it not the same as muscle?
This is the most important point for understanding the findings. Lean body mass includes all body weight that is not fat: skeletal muscle, internal organs, bones, fluids and other tissues. In other words, muscle is only part of it.
So when a DXA scan, a low-dose X-ray scan that measures body composition, shows a drop, not all of it is muscle loss. Changes in fluids and in glycogen, the form in which sugar is stored in the liver and muscle, also affect the measurement. Still, studies use this measure as an indirect marker of muscle health. So a significant drop in it calls for attention.
How much lean body mass did patients lose on treatment?
In the pooled analysis, GLP-1 treatment was linked to an average loss of 1.74 kg of lean mass compared with placebo. Relative to baseline, the drop was 3.06%. On the other hand, the researchers found a rise of 1.81 percentage points in the share of lean mass in total body weight.
The meaning is simple. Patients lost a little lean mass, but they lost far more fat. As a result, the ratio of lean mass to weight improved, and body composition became healthier. In other words, some loss of lean mass does not mean the treatment harms body composition.
Semaglutide: large losses in weight and in lean mass
Among the drugs studied, semaglutide 2.4 mg a week was linked to the largest loss. The data showed an average loss of 5.44 kg of lean mass, a 9.9% drop from baseline.
However, we need to read this figure with caution. First, semaglutide also led to a particularly large loss of weight and fat. Second, the data on it came from a single trial, the STEP 1 trial, and from a small scanned subgroup. In addition, the researchers calculated how much of the weight lost was lean mass. With liraglutide the share was 14% to 22%. With semaglutide it reached up to 45%, and with tirzepatide about 26%.
These differences may reflect the size of the weight loss, the length of treatment, different populations and different measuring methods. So we cannot conclude from them that one drug “harms muscle” in particular.
What did we learn about tirzepatide?
With tirzepatide, too, researchers saw a drop in lean mass. The SURMOUNT-1 trial tested the drug in 2,539 adults with obesity. The SURMOUNT-1 DXA substudy included 160 patients. After 72 weeks, weight fell by 21.3%, fat by 33.9% and lean mass by 10.9%. In the placebo group the drops were 5.3%, 8.2% and 2.6%, respectively.
In other words, the fat loss was about three times larger than the lean mass loss. Across both groups, about 75% of the weight lost was fat and about 25% was lean mass. So with tirzepatide, too, body composition improved. The meta-analysis’s statistical analysis left out the tirzepatide data, because the researchers did not obtain detailed enough data on the subgroup.
Do these drugs cause sarcopenia?
The study cannot answer that. Sarcopenia, the loss of muscle mass and strength, depends not only on the amount of muscle. It also includes muscle strength and physical function.
The studies in the review did not measure grip strength, walking speed, rising from a chair or endurance. So there is not yet a full answer to whether the loss of lean mass also harmed strength and function. This is one of the paper’s important limitations. A drop measured on a scan is not necessarily a clinical injury to muscle.
Lean body mass falls with any weight loss
It is worth remembering a simple fact. Almost any substantial weight loss comes with some loss of lean mass, whether through diet, medication or bariatric surgery. Even in the placebo groups, who received diet and activity advice, lean mass fell.
According to the researchers, the rate with GLP-1 drugs is similar to that seen after bariatric surgery. Earlier meta-analyses estimated that about 25% to 30% of the weight lost on these drugs is lean mass. Another 2026 meta-analysis, covering 36 studies, also found that most of the loss comes from fat, and the drop in lean mass is moderate. So the goal is not to prevent every loss. The goal is to limit muscle loss, maintain strength and function, and make sure most of the loss comes from fat.
Protein and strength training are part of treatment
The researchers’ practical conclusion is clear. Obesity drug treatment should include nutritional support and physical activity to preserve muscle. Enough protein gives the body its building blocks. At the same time, resistance training signals the muscle to preserve itself, even during weight loss.
The drug reduces hunger, and sometimes patients eat very little. In that case, there is a risk they will not get enough protein and energy. So it is not enough to say “I eat less”. You need to check what you eat. Practical guidance appears in my article on preserving muscle mass during weight loss and in my nutrition guide for weight loss injections.
Should you measure body composition?
The paper reinforces the importance of a broad assessment beyond weight. The scale does not tell how much fat was lost, how much lean mass was kept, or what happened to physical capacity. Tests such as DXA or BIA, bioelectrical impedance, give information on trends. However, doctors should read them in clinical context, because they do not measure pure muscle.
At the same time, it is worth tracking functional measures: grip strength, rising from a chair, walking speed, balance and endurance. Sometimes function matters more than the number in a body composition report.
Who needs follow-up most?
Most participants were relatively young, with average ages of 31 to 51, without diabetes and with few other conditions. So we cannot be sure the findings are the same in older age, frailty, diabetes or low muscle mass to begin with. In these groups the risk of significant muscle loss may be higher. So it is important to combine assessment of nutrition, activity, body composition and strength.
Research in this field keeps moving. For example, drug companies are now developing drugs designed to preserve muscle during weight loss. The higher-dose semaglutide data from the STEP UP trial also add MRI findings on thigh muscle and function.
The bottom line on lean body mass and GLP-1 drugs
GLP-1 drugs at obesity doses lead to a large loss of fat and better body composition. Alongside this, there is also some loss of lean body mass. The findings do not justify avoiding treatment. However, they remind us that kilograms alone do not measure success.
Ultimately, the goal is to lose mainly fat, preserve muscle and improve health and function. So a protein-rich diet, strength training and body composition follow-up are not a minor extra. They are an integral part of treatment.
This article provides general information and is not a substitute for personal medical advice.
References
Once-Weekly Semaglutide in Adults with Overweight or Obesity
