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Muscle and grip: the mass went down and the strength did not

Skeletal muscle mass fell over twelve months on semaglutide. Handgrip strength was unchanged, and the metabolic slowdown happened in the comparison group too.

Dana Sullivan7 min read
Twelve months on semaglutide — what movedskeletal muscle29.9 kg28.7 kgfat-free mass53.8 kg52.7 kghandgrip strengthpreservedMetabolic rate fell past prediction — in both groups alike44 on semaglutide, 39 on lifestyle alone. One center, not randomized.

Two measurements in this study disagree with each other, and the disagreement is more useful than either one alone: the muscle got smaller and the hand did not get weaker. What the lean-mass numbers mean is covered elsewhere on this site; this is about what happens when somebody also measures what the muscle can do.

The setup

A single obesity unit in Barcelona, looking back at routine care between January 2024 and December 2025. [1] Adults with a body mass index of 30 or more and no diabetes, 44 on semaglutide alongside a lifestyle program and 39 on the program alone, each with a baseline and a twelve-month assessment.

Nobody was randomized. In routine care the people who end up on a drug differ from the people who do not, and 83 patients at one center is a small base for any of it.

What came off

Weight fell 11.0 kg further in the semaglutide group, p = 0.001, with body mass index down 4.0 and waist circumference down 7.0 cm, p = 0.002.

Fat mass fell. So did skeletal muscle mass, from 29.9 to 28.7 kg, and fat-free mass, from 53.8 to 52.7 kg, both at p < 0.001. That is the finding people argue about, and it is real here. Losing weight costs lean tissue by whatever route it happens; what a drug adds on top is the open question, and it is the same shape of question as what a higher dose buys and what it costs.

The adaptation that was not the drug

Resting energy expenditure fell in both groups by more than fat-free mass, fat mass, age and sex would predict — the phenomenon called adaptive thermogenesis, the body spending less than its new size implies.

There was no significant difference between the groups. The semaglutide patients lost far more weight and their metabolic rate adapted no differently from the people who lost less without the drug. That is worth stating carefully, because it would be easy and wrong to file it as a GLP-1 side effect. It is what losing weight does, and this study found the drug neither caused it nor prevented it.

What a reader takes from it

That the muscle question needs a strength test attached to it, and almost never gets one. A study reporting kilograms of lean mass and stopping there has measured half of the thing people actually care about.

And that the metabolic adaptation is going to be there whatever route you take down, which is part of why weight comes back after stopping. None of this is settled by 83 people at one hospital, and the authors’ own conclusion is a request for better monitoring rather than a claim — the appropriate weight for an observation from routine care.

Frequently asked

Does semaglutide cost you muscle?
Skeletal muscle mass fell from 29.9 to 28.7 kg over twelve months here. Handgrip strength did not change, so the mass and the function moved differently.
Does it slow your metabolism?
Resting energy expenditure fell further than body composition predicts — but equally in the group losing weight without the drug. This study found no difference between them.
How big was the study?
83 patients at one hospital, 44 on semaglutide and 39 on lifestyle alone, looked at retrospectively rather than randomized.
Why did one muscle measure improve while mass fell?
The improving measure is a reference-standardized score comparing a person against norms for their age and body size, not against their own earlier kilograms.

Sources

  1. [1] Filippi-Arriaga F, et al. (2026). Longitudinal Changes in Body Composition, Adaptive Thermogenesis and Muscle Strength in Patients with Obesity Treated with Semaglutide Obesity Facts. PMID 42640861

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