Weight loss with GLP-1 medicines does not result in a disproportionate loss of muscle mass or function in obese mice and humans
Open accessAbstract
The large decrease in body weight with glucagon-like peptide-1 (GLP-1) medicines raises concern about a loss of lean body mass (LBM) and skeletal muscle. In this work, we present four pre-clinical studies and a proof-of-concept clinical trial that address this issue. We report that in obese mice, GLP-1 medicines predominantly reduce body fat alongside a small but significant decrease in LBM. Among lean tissues, loss of liver mass exceeds change in muscle mass. While absolute muscle mass and strength decrease, relative muscle mass and strength improve, resulting in better running performance. Interestingly, while atrophy is similar during immobilization, GLP-1 medicines have a distinct effect on the muscle proteome compared to calorie restriction. Patients with obesity on GLP-1 medicines improve their body composition without negatively affecting strength. Overall, in middle-aged mice and men, GLP-1 medicines slightly decrease absolute muscle values but positively impact body composition and mobility. The clinical trial is registered on clinicaltrials.gov (NCT05606471).
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Available evidence suggests that changes in lean mass during GLP-1-induced weight loss are largely proportional to overall weight loss and may reflect adaptive physiological responses rather than pathological muscle loss.
“available evidence suggests that these changes are largely proportional to overall weight loss and may reflect adaptive physiological responses rather than pathological muscle loss”
From Weight maintenance after discontinuation of GLP-1 therapies (2026) · cites this paper as [70]
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Macêdo, A. P. A., de Mattis, L. R. D. C., de Lima, R. D., Barbosa, L. A., Pinotti, C. B., Brisque, G. D., Dias, L. M., Pitoli, B. D. S., Avelino, A. A., Antonio, G. C. F., et al. (2026) · The Journal of Physiology · doi:10.1113/jp291770
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- Authors
- Langer, H. T., Gilmore, N. K., Hayden, C. M. T., Roux, J., Bariohay, B., Rouquet, T., Awada, M., Marcotorchino, J., Bournot, L., Nunn, E., Titchenell, P. M., Liskiewicz, D., Müller, T. D., Anyiam, O., Atherton, P. J., Idris, I., Hentschel, A., Roos, A., Haritonow, N., Norman, K., Müller-Werdan, U., & Baar, K.
- Affiliations
- Humboldt-Universität zu Berlin (DE)
- University of California, Davis (US)
- University of Pennsylvania (US)
- Helmholtz Munich (DE)
- University of Nottingham (GB)
- Ritsumeikan University (JP)
- Leibniz Institute for Analytical Sciences - ISAS (DE)
- Children's Hospital of Eastern Ontario (CA)
- Corresponding author
- Langer, Henning Tim
- ORCID
- Venue
- Cell Reports Medicine
- Publisher
- Elsevier BV
- Published
- 2026-03
- Volume
- 7
- Issue
- 3
- Pages
- 102665
- ISSN
- 2666-3791 (ISSN-L)
- PMC
- PMC13006392
- OpenAlex
- W7137854865
- Cited by
- 21
- References
- 53
- Citations by year
- 2026: 21
- FWCI
- 96.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports Medicine (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by-nc-nd)
- Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
- Funders
- Ministerium für Kultur und Wissenschaft des Landes Nordrhein-Westfalen
- Bundesministerium für Forschung, Technologie und Raumfahrt
- Institute of Space and Astronautical Science
- UC Davis (T32 GM144303)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK139663, DK139565)
- Topics
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- GLP-1 receptor agonists, weight loss, obesity, lean body mass, skeletal muscle mass, muscle strength, muscle atrophy, body composition, liver mass, muscle proteome, caloric restriction, immobilization, running performance, mobility (physical function)
- MeSH terms
- Adipose Tissue, Adult, Animals, Body Composition, Female, Humans, Male, Mice, Inbred C57BL, Mice, Obese, Middle Aged, Obesity, Weight Loss, Muscle, Skeletal, Mice, Glucagon-Like Peptide 1, Muscle Strength
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