AMRA Medical AB, Linköping, Sweden (J.L.).
Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Sweden (J.L.).
Circulation. 2024 Oct 15;150(16):1288-1298. doi: 10.1161/CIRCULATIONAHA.124.067676. Epub 2024 Oct 14.
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.
最近的研究表明，胰高血糖素样肽-1 受体激动剂（GLP-1 RAs）和联合疗法的药物减肥效果接近手术减肥的效果。然而，随着减肥效果的提高，人们担心可能会对肌肉数量、组成和功能产生潜在的不良影响。本指南旨在探讨 GLP-1 RA 等减肥治疗相关的肌肉变化是否可能是适应不良的（即，对肌肉健康或功能产生不利影响）、适应的（即，对减肥的生理反应，维持或最小程度地影响肌肉健康或功能），或者可能是减肥的增强反应（即，治疗后改善肌肉健康或功能）。基于当代证据，并结合使用磁共振成像的研究，GLP-1 RA 治疗引起的骨骼肌变化似乎是适应的：肌肉体积 z 评分的变化表明肌肉体积发生了变化，与衰老、疾病状态和减肥效果相一致，而胰岛素敏感性和肌肉脂肪浸润的改善可能有助于适应过程，改善肌肉质量，降低力量和功能丧失的可能性。然而，由于肌肉减少症的风险，年龄较大和衰弱前期等因素可能会影响这些治疗的合适候选者的选择。几种旨在与 GLP-1 为基础的治疗相结合以维持或改善肌肉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），以及为了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、组成、功能、活动能力和力量的准确和有意义的评估）对于未来很可能会服用这些药物的大量患者非常重要。
