Recent studies have shown that pharmacologic weight loss with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and combination therapies is approaching magnitudes achieved with surgery. However, as more weight loss is achieved, there is concern for potential adverse effects on muscle quantity, composition, and function. This primer aims to address whether muscle-related changes associated with weight loss treatments such as GLP-1 RAs may be maladaptive (ie, adversely affecting muscle health or function), adaptive (ie, a physiologic response to weight loss maintaining or minimally affecting muscle health or function), or perhaps an enhanced response to weight loss (ie, improved muscle health or function after treatment). Based on contemporary evidence with the addition of studies using magnetic resonance imaging, skeletal muscle changes with GLP-1 RA treatments appear to be adaptive: changes in muscle volume z-score indicate a change in muscle volume that is commensurate with what is expected given aging, disease status, and weight loss achieved, and the improvement in insulin sensitivity and muscle fat infiltration likely contributes to an adaptive process with improved muscle quality, lowering the probability for loss in strength and function. Nevertheless, factors such as older age and prefrailty may influence the selection of appropriate candidates for these therapies because of risk for sarcopenia. Several pharmacologic treatments to maintain or improve muscle mass designed in combination with GLP-1-based therapies are under development. For future development of GLP-1-based therapies (and other therapies) designed for weight loss, as well as for patient-centered treatment optimization, the introduction of more 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 substantial numbers of patients who will likely be taking these medications well into the future.

中文翻译：

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肌肉质量和胰高血糖素样肽-1 受体激动剂：对体重减轻的适应性反应还是适应不良反应？


最近的研究表明，胰高血糖素样肽-1 受体激动剂 （GLP-1 RAs） 和联合疗法的药理学体重减轻正在接近手术实现的幅度。然而，随着体重减轻的增加，人们担心对肌肉数量、成分和功能的潜在不利影响。本入门指南旨在解决与减肥治疗（如 GLP-1 RAs）相关的肌肉相关变化是否可能是适应不良（即对肌肉健康或功能产生不利影响）、适应性（即对减肥的生理反应维持或对肌肉健康或功能的影响最小），或者可能是对体重减轻的增强反应（即治疗后肌肉健康或功能得到改善）。根据当代证据以及使用磁共振成像的研究，GLP-1 RA 治疗的骨骼肌变化似乎是适应性的：肌肉体积 z 评分的变化表明肌肉体积的变化与给定衰老、疾病状况和体重减轻的预期相称，胰岛素敏感性和肌肉脂肪浸润的改善可能有助于改善肌肉质量的适应性过程， 降低力量和功能丧失的可能性。然而，由于存在肌肉减少症的风险，高龄和虚弱等因素可能会影响这些疗法的合适人选的选择。几种与基于 GLP-1 的疗法相结合的维持或改善肌肉质量的药物治疗正在开发中。 为了未来开发基于 GLP-1 的减肥疗法（和其他疗法）以及以患者为中心的治疗优化，引入更客观和全面的肌肉健康评估方法（包括对肌肉数量、成分、功能、活动性和力量的准确和有意义的评估）对于未来可能服用这些药物的大量患者非常重要。