{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:00:22Z","timestamp":1786118422910,"version":"build-2736575974"},"reference-count":0,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiorenal Med"],"abstract":"<jats:p>Background\nPreserving lean body mass (LBM) is increasingly recognized as a critical determinant of survival and disease progression in individuals with cardiovascular\u2013kidney\u2013metabolic (CKM) syndrome. Sarcopenia is significantly associated with higher risk of all-cause, cardiovascular (CVD), and non-CVD mortality, as well as greater odds of advancing to later CKM stages. While incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1\/gastric inhibitory polypeptide (GIP) receptor agonists, are now cornerstones of CKM management, emerging evidence suggests a potential association with loss of LBM and skeletal muscle in vulnerable patients. The key gap in knowledge is that most trials and real-world evaluations prioritize weight and cardio\u2013kidney\u2013metabolic endpoints, while muscle mass, strength, functional trajectories, frailty progression, and patient-reported impacts are inconsistently measured, especially in high-risk CKM populations. This review synthesizes clinical trial and real-world evidence to characterize body composition changes with incretin-based therapies and proposes a conceptual, stepwise framework to maintain patient-centered muscle health. PubMed, Scopus, and Web of Science were searched for English-language peer-reviewed studies (January 2004\u2013January 2026) evaluating incretin-based therapies and LBM outcomes; ClinicalTrials.gov and WHO ICTRP were also queried for trials with muscle-related endpoints.\nSummary\nAcross incretin agents, weight loss is typically fat-predominant; however, available studies suggest approximately 25\u201339% of total weight loss may reflect LBM reduction over 36\u201372 weeks. Major evidence gaps include: (1) limited longitudinal data linking LBM loss to strength, mobility, frailty, falls, disability, and patient-reported function; (2) sparse head-to-head comparisons to clarify agent- and dose-specific muscle effects across the CKM continuum; (3) underrepresentation of high-risk CKM subgroups most vulnerable to protein-energy wasting, anabolic resistance, and polypharmacy; and (4) lack of scalable risk prediction and monitoring tools to detect early adverse body-composition trajectories.\nKey Messages \nDespite rapid expansion of incretin-based therapies across the CKM continuum, muscle health is rarely measured, yet it strongly shapes survival, frailty, and functional independence. Muscle preservation is a key consideration in benefit\u2013risk assessment and merits explicit tracking in both clinical trials and routine practice. We outline a patient-centered, stepwise roadmap that pairs incretin prescribing with baseline muscle-risk characterization, serial tracking of body composition (e.g., DXA\/BIA\/BIS where feasible), simple functional measures, and early mitigation strategies (resistance training, nutrition optimization, and, when appropriate, adjunct anabolic\/anti-catabolic approaches). Priorities to advance the field include pragmatic long-term studies in high-risk CKM populations and standardized capture of functional and patient-reported outcomes.<\/jats:p>","DOI":"10.1159\/000553166","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T16:01:06Z","timestamp":1786032066000},"page":"1-28","source":"Crossref","is-referenced-by-count":0,"title":["Muscle Health in the Era of Incretin-Based Weight Loss: Implications for Patients with Cardiovascular-Kidney-Metabolic Syndrome"],"prefix":"10.1159","author":[{"given":"Niloofar","family":"Nobakht","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1976-6789","authenticated-orcid":false,"given":"Taraneh","family":"Mousavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooneh","family":"Jabbaripour Sarmadian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1674-9342","authenticated-orcid":false,"given":"Mohammad","family":"Kamgar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,8,6]]},"container-title":["Cardiorenal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000553166","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T16:01:06Z","timestamp":1786032066000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000553166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,6]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1159\/000553166","archive":["Portico"],"relation":{},"ISSN":["1664-3828","1664-5502"],"issn-type":[{"value":"1664-3828","type":"print"},{"value":"1664-5502","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,6]]}}}