Weight loss with GLP-1 medicines does not result in a disproportionate loss of muscle mass or function in obese mice and humans

Henning Tim Langer; Natalie K Gilmore; Christopher M T Hayden; Julien Roux; Bruno Bariohay; Thaïs Rouquet; Manar Awada; Julie Marcotorchino; Lorrine Bournot; Elizabeth Nunn; Paul M Titchenell; Daniela Liskiewicz; Timo D Müller; Oluwaseun Anyiam; Philip J Atherton; Iskandar Idris; Andreas Hentschel; Andreas Roos; Natalie Haritonow; Kristina Norman; Ursula Müller-Werdan; Keith Baar

doi:10.1016/j.xcrm.2026.102665

Weight loss with GLP-1 medicines does not result in a disproportionate loss of muscle mass or function in obese mice and humans

Cell Rep Med. 2026 Mar 17;7(3):102665. doi: 10.1016/j.xcrm.2026.102665.

Authors

Henning Tim Langer¹, Natalie K Gilmore², Christopher M T Hayden², Julien Roux³, Bruno Bariohay³, Thaïs Rouquet³, Manar Awada³, Julie Marcotorchino³, Lorrine Bournot³, Elizabeth Nunn⁴, Paul M Titchenell⁴, Daniela Liskiewicz⁵, Timo D Müller⁵, Oluwaseun Anyiam⁶, Philip J Atherton⁷, Iskandar Idris⁶, Andreas Hentschel⁸, Andreas Roos⁹, Natalie Haritonow¹⁰, Kristina Norman¹¹, Ursula Müller-Werdan¹⁰, Keith Baar¹²

Affiliations

¹ Department of Geriatrics and Medical Gerontology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. Electronic address: henning-tim.langer@charite.de.
² Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, CA, USA.
³ Biomeostasis, Marseille, France.
⁴ Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
⁵ Institute for Diabetes and Obesity, Helmholtz Munich, German Center for Diabetes Research (DZD) and Walther Straub Institute for Pharmacology and Toxicology, Ludwig-Maximilians University Munich, Munich, Germany.
⁶ Centre of Metabolism, Ageing & Physiology, MRC/Versus Arthritis Centre of Excellence for Musculoskeletal Research, NIHR Biomedical Research Centre (BRC), University of Nottingham, Royal Derby Hospital Medical School, Derby, UK.
⁷ Centre of Metabolism, Ageing & Physiology, MRC/Versus Arthritis Centre of Excellence for Musculoskeletal Research, NIHR Biomedical Research Centre (BRC), University of Nottingham, Royal Derby Hospital Medical School, Derby, UK; Faculty of Sport and Health Science, Ritsumeikan Advanced Research Academy (RARA), Ritsumeikan University, Kyoto, Japan.
⁸ Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Dortmund, Germany.
⁹ Department of Neuropediatrics and Neuromuscular Centre for Children and Adolescents, University Hospital Essen, Duisburg-Essen University, Essen, Germany; Brain and Mind Research Institute, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada.
¹⁰ Department of Geriatrics and Medical Gerontology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
¹¹ Department of Geriatrics and Medical Gerontology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam Rehbrücke, Nuthetal, Germany.
¹² Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, CA, USA; Department of Physiology and Membrane Biology, University of California, Davis Health, Davis, CA, USA.

Abstract

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).

Keywords: GLP-1; atrophy; function; incretins; muscle loss; muscle mass; obesity; wasting; weight loss.

MeSH terms

Adipose Tissue / drug effects
Adult
Animals
Body Composition / drug effects
Female
Glucagon-Like Peptide 1* / pharmacology
Glucagon-Like Peptide 1* / therapeutic use
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Obese
Middle Aged
Muscle, Skeletal* / drug effects
Muscle, Skeletal* / pathology
Muscle, Skeletal* / physiopathology
Obesity* / drug therapy
Obesity* / pathology
Obesity* / physiopathology
Weight Loss* / drug effects

Substances

Glucagon-Like Peptide 1

Associated data

ClinicalTrials.gov/NCT05606471