The recently published primer summarizes contemporary evidence indicating that muscle composition changes associated with GLP-1-based therapies appear to be adaptive
LINKÖPING, Sweden, October 16, 2024 – A focused review titled "Muscle Mass and Glucagon-like Peptide-1 Receptor Agonists: Adaptive or Maladaptive Response to Weight Loss?" was recently published in the renowned cardiovascular scientific journal, Circulation. Authored by AMRA Medical's Dr. Jennifer Linge, professor Andreas Birkenfeld of University Hospital Tübingen, and associate professor Ian Neeland of University Hospitals Cleveland, the article discusses several aspects of the response associated with weight loss with respect to muscle health.
As pharmaceutical treatments, such as GLP-1 agonists, are reaching weight reductions of magnitudes close to those achieved through bariatric surgery, the concerns regarding a possible adverse impact on muscle health are growing. In light of this, the experts aimed to address whether muscle-related changes associated with weight loss treatments such as GLP-1 receptor agonists may be maladaptive (i.e., adversely impacting muscle health/function), adaptive (i.e., a physiologic response to weight loss maintaining or minimally affecting muscle health/function), or perhaps an enhanced response to weight loss (i.e., improved muscle health/function following treatment).
Historical studies of GLP-1-based therapies and body composition have reported absolute and/or relative changes in total body lean mass. Results vary greatly from study to study, likely due to, e.g., variations in population characteristics, study durations, and dosing, but also because of the individual heterogeneity in lean mass composition - comprising not only muscle mass, but also organs, bone, fluids, and water in fat tissue.
The heterogeneity in past study results makes it difficult for clinicians and researchers to determine what is "normal" or "healthy" weight reduction. However, recent studies in this area have utilized gold-standard MRI-based technology and muscle composition assessments including muscle volume (both in liters and as a sex-, height-, weight-, and BMI invariant z-score describing 'relative or adequate muscle mass') as well as muscle fat infiltration, providing muscle-specific data on the effect of incretin-based treatments. The authors conclude that the introduction of objective and comprehensive ways of assessing muscle health (including accurate and meaningful assessments of muscle quantity, composition, function, mobility, and strength) is important for the future development of GLP-1-based therapies and patient-centric treatment optimization.
As drug development activity increases in the obesity indication and branches out towards aiming for weight reduction with preserved muscle health, it is paramount to include measures such as the muscle volume z-score and muscle fat infiltration, in order to understand the safety and benefit of drugs achieving significant and/or rapid weight reduction. AMRA is committed to pioneering not only the development of powerful biomarker methodologies such as the muscle volume z-score in order to augment drug development, but also to the generation of normative data, providing context to future clinical trials and basis for interpretation of clinical benefits related to improving/maintaining muscle health. These initiatives will help ensure that the obesity field develops products with safety and the impact on vulnerable populations in mind.
You can read the full article to learn more about MRI-based muscle assessment and its use in determining the relationship between drug-induced weight reduction and muscle health here.
Follow AMRA on LinkedIn for the latest updates in body composition and how the use of MRI-based fat distribution and muscle composition analysis is advancing disease research in metabolic diseases including obesity, and beyond.
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