The dual challenge of weight management: assessing the impact of GLP-1 receptor agonists on lean body mass in global clinical trials (2020–2025)
Keywords:
BODY COMPOSITION; DRUG THERAPY; GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS; WEIGHT LOSS.; COMPOSICIÓN CORPORAL; QUIMIOTERAPIA; AGONISTAS RECEPTOR DE PÉPTIDOS SIMILARES AL GLUCAGÓN; PÉRDIDA DE PESO.; COMPOSIÇÃO CORPORAL; TRATAMENTO FARMACOLÓGICO; AGONISTAS DO RECEPTOR DO PEPTÍDEO 1 SEMELHANTE AO GLUCAGON; REDUÇÃO DE PESO.Abstract
Introduction: glucagon-like peptide-1 receptor agonists have revolutionized the pharmacological treatment of obesity; however, their use has raised concern regarding the concomitant loss of lean body mass, with potential metabolic and functional implications.
Objective: to evaluate the magnitude of lean body mass loss associated with glucagon-like peptide-1 receptor agonists and to assess effective strategies for its mitigation.
Methods: a systematic review was conducted in accordance with the PRISMA statement. Multiple databases were searched, and sources published between 2020 and 2025 that met the selection criteria were identified. Following study selection, data extraction was performed, and the risk of bias was assessed using the Cochrane RoB 2 tool.
Development: lean body mass loss represents a substantial and disproportionate fraction of total weight loss (approximately 25–40%), a pattern consistently observed across different agents. Negative energy balance and reduced protein intake contribute predominantly to this phenomenon. Studies incorporating resistance training and higher protein intake demonstrated a significant reduction in the proportion of lean body mass lost.
Conclusions: glucagon-like peptide-1 receptor agonists induce effective weight loss but are accompanied by a relevant reduction in lean body mass. The mandatory integration of exercise and high-protein nutritional strategies is therefore recommended to optimize the quality of weight loss and reduce associated clinical risks.
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