Fundamental Body Composition Principles Provide Context for Fat-Free and Skeletal Muscle Loss With GLP-1 RA Treatments

During weight loss, reductions in body mass are commonly described using molecular body components (eg, fat mass and fat-free mass [FFM]) or tissues and organs (eg, adipose tissue and skeletal muscle). While often conflated, distinctions between body components established by different levels of the 5-level model of body composition-which partitions body mass according to the atomic, molecular, cellular, tissue/organ, or whole-body level-are essential to recall when interpreting the composition of weight loss. A contemporary area of clinical and research interest that demonstrates the importance of these concepts is the discussion surrounding body composition changes with glucagon-like peptide-1 receptor agonists (GLP-1RA), particularly in regard to changes in FFM and skeletal muscle mass. The present article emphasizes the importance of fundamental principles when interpreting body composition changes experienced during weight loss, with a particular focus on GLP-1RA drug trials. The potential for obligatory loss of FFM due to reductions in adipose tissue mass and distribution of FFM loss from distinct body tissues are also discussed. Finally, selected countermeasures to combat loss of FFM and skeletal muscle, namely resistance exercise training and increased protein intake, are presented. Collectively, these considerations may allow for enhanced clarity when conceptualizing, discussing, and seeking to influence body composition changes experienced during weight loss.