Semaglutide can help people with obesity lose a substantial amount of weight, but some of that loss may come from muscle and other lean tissue rather than fat.
New research suggests that older adults, women and people who eat less protein may be especially likely to lose lean mass while taking the drug.
Semaglutide belongs to a group of medicines known as GLP-1 drugs. It copies the action of a natural hormone involved in appetite and blood sugar control, helping people feel full sooner and eat less.
The medicine is used in different forms to treat type 2 diabetes and obesity. Its ability to produce major weight loss has changed obesity treatment, but researchers are increasingly interested in what kind of body tissue people lose along with the kilograms.
Losing weight almost always involves some loss of lean mass, which includes muscle as well as other non-fat tissues. Preserving muscle is important because muscles support movement, strength, balance, bone health and the body’s ability to use glucose from the blood.
Researchers led by Dr. Melanie Haines of Massachusetts General Hospital and Harvard Medical School studied 40 adults with obesity for three months. Twenty-three participants received semaglutide, while 17 took part in a lifestyle program called Healthy Habits for Life.
The team measured changes in body composition rather than looking only at total body weight. This allowed the researchers to estimate how much of the weight participants lost came from lean tissue.
People taking semaglutide lost more weight overall than those following the lifestyle program. However, in both groups, about 40% of the weight lost was lean mass, showing that changes in body composition deserve attention during weight-loss treatment.
Within the semaglutide group, the researchers found that women and older participants tended to lose more lean mass. Lower protein intake was also associated with greater lean mass loss.
Protein provides the building blocks the body needs to maintain and repair muscle. When people eat much less because their appetite is reduced, getting enough protein and other nutrients can become more difficult unless meals are planned carefully.
The study also found a possible connection between muscle preservation and blood sugar control. Participants who lost more lean mass showed smaller improvements in HbA1c, a blood test that reflects average blood sugar levels over the previous few months.
That finding is important because skeletal muscle helps remove glucose from the bloodstream and use it for energy. Losing too much muscle could therefore affect some of the metabolic improvements people hope to gain from weight loss.
The researchers said adequate protein intake may be one possible way to help protect lean mass during semaglutide treatment. Resistance exercise, such as strength training, is also widely used to help maintain muscle during weight loss, although this small study was not designed to determine the best muscle-preserving program.
The research was presented at ENDO 2025, the Endocrine Society’s annual meeting, held in San Francisco. Because conference findings may be preliminary and the study involved only 40 people over three months, larger and longer studies are needed before firm conclusions can be drawn.
Future research will need to determine how age, sex, diet, exercise and the amount of weight lost influence muscle changes during GLP-1 treatment. Scientists also want to learn how much lean mass loss is clinically important and which strategies protect muscle most effectively.
For people taking semaglutide, the findings do not mean the medicine should be avoided or stopped. Instead, they highlight the importance of looking beyond the number on the scale and discussing nutrition, physical activity and healthy body composition with a healthcare professional during treatment.
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