Muscle Mass Loss With GLP-1 Receptor Agonists: Pharmacotherapy-Induced Sarcopenia and Mitigation Strategies
DOI:
https://doi.org/10.66201/ss.v1.23Keywords:
Sarcopenia, GLP-1 Agonists, Semaglutide, Tirzepatide, Muscle Mass, Resistance Exercise, Sarcopenic Obesity, Body CompositionAbstract
Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/GIP agonists represent an unprecedented therapeutic advance in the management of obesity and type 2 diabetes. An emerging risk is the loss of fat-free mass (FFM) associated with weight reduction. Semaglutide shows an FFM loss corresponding to 40%–45% of total weight loss, whereas tirzepatide decreases to 25%, indicating mechanistic differences. This study aims to summarize the evidence regarding: (a) the magnitude and chronology of muscle loss with each GLP-1 RA agonist; (b) interventions to mitigate it; and (c) variability in risk among vulnerable populations.
Methods: A systematized integrative review was conducted according to the PRISMA 2020 guidelines, with searches performed in the PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and Web of Science databases for the period January 2020–March 2026. Twenty studies meeting the eligibility criteria were included, comprising randomized clinical trials, meta-analyses, systematic reviews, and observational studies.
Results: FFM loss with GLP-1 RAs ranged from 15% to 60% of total weight loss, with high heterogeneity among studies. Progressive resistance training (≥ 2 sessions/week) and adequate protein intake (1.2–1.6 g/kg/day) are the strategies with the strongest evidence for attenuating FFM loss. Older adults (≥ 60 years), patients with chronic kidney disease, and post-bariatric patients show greater vulnerability.
Conclusions: Muscle mass loss associated with GLP-1 analogs is a real, variable, and clinically relevant phenomenon, especially in vulnerable populations. The standard of care includes resistance training, protein supplementation, and precise monitoring of body composition.
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Copyright (c) 2026 Albert Rafael Barrail Hellman, Diego Javier Alvarez Marecos, Andrea Dionisia Franco, Ninive Urunaga Romero, Patricia Lais Frighetto Nodari, Ana Isabel Martínez Marmori, Lida Romina Miranda (Autor/a)
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