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Moreover, robust cardiometabolic benefits and favorable safety profiles have positioned GLP-1RAs at the forefront of modern obesity pharmacotherapy. However, findings from large-scale trials (eg, SUSTAIN, STEP, SURPASS) have raised concerns that a significant proportion of the weight loss achieved with GLP-1RA treatment may derive from lean body mass\u2014particularly skeletal muscle\u2014which could be detrimental in populations already at risk for sarcopenia. However, emerging preclinical evidence suggests that GLP-1RAs may directly and indirectly influence skeletal muscle through anti-inflammatory, antioxidant, and mitochondrial-supportive mechanisms. These include modulation of key signaling pathways such as PI3K\/Akt\/mammalian target of rapamycin (mTOR) and AMP-activated protein kinase\u2013PGC-1\u03b1, suppression of proteolytic activity, and promotion of myogenic differentiation. In experimental models of aging, sarcopenic obesity, and chronic disease, GLP-1RAs have shown muscle-preserving properties. Nevertheless, the balance between adipose tissue reduction and lean mass preservation remains incompletely understood in clinical settings. This review examines the existing experimental and clinical evidence and identify critical research directions to determine whether GLP-1RAs confer overall benefit or carry unintended risks for skeletal muscle integrity in the context of weight loss.<\/jats:p>","DOI":"10.1093\/ejendo\/lvaf223","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T13:08:01Z","timestamp":1761743281000},"page":"R31-R44","source":"Crossref","is-referenced-by-count":18,"title":["Glucagon-like peptide-1 receptor agonists and muscle health: potential role in sarcopenia prevention and treatment"],"prefix":"10.1093","volume":"193","author":[{"given":"Ainhoa","family":"Gonz\u00e1lez-Luis","sequence":"first","affiliation":[{"name":"Research Unit, University Hospital Nuestra Se\u00f1ora de Candelaria (UHNSC) , Santa Cruz de Tenerife 38010 ,","place":["Spain"]},{"name":"Doctoral and Graduate School, University of La Laguna , San Crist\u00f3bal de La Laguna 38200 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de Candelaria (UHNSC) , Santa Cruz de Tenerife 38010 ,","place":["Spain"]},{"name":"GEENDIAB (Grupo Espa\u00f1ol Para el Estudio de la Nefropat\u00eda Diab\u00e9tica), Sociedad Espa\u00f1ola de Nefrolog\u00eda , Santander 39000 ,","place":["Spain"]},{"name":"RICORS2040 (RD24\/004\/0022), Instituto de Salud Carlos III , Madrid 28000 ,","place":["Spain"]},{"name":"Instituto de Tecnolog\u00edas Biom\u00e9dicas, Universidad de La Laguna , Santa Cruz de Tenerife 38000 ,","place":["Spain"]},{"name":"Nephrology Service, University Hospital Nuestra Se\u00f1ora de Candelaria (UHNSC) , Santa Cruz de Tenerife 38010 ,","place":["Spain"]},{"name":"Facultad de Ciencias de la Salud, Universidad Fernando Pessoa Canarias , Las Palmas de Gran Canaria 35450 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