Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Division of Cardiovascular Medicine, University Hospitals Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
Diabetes Obes Metab. 2024 Sep;26 Suppl 4:16-27. doi: 10.1111/dom.15728. Epub 2024 Jun 27.
Weight loss induced by glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucagon-like peptide-1 receptor (GLP-1R)/glucose-dependent insulinotropic polypeptide receptor agonists is coming closer to the magnitudes achieved with surgery. However, with greater weight loss there is concern about potential side effects on muscle quantity (mass), health and function. There is heterogeneity in the reported effects of GLP-1-based therapies on lean mass changes in clinical trials: in some studies, reductions in lean mass range between 40% and 60% as a proportion of total weight lost, while other studies show lean mass reductions of approximately 15% or less of total weight lost. There are several potential reasons underlying this heterogeneity, including population, drug-specific/molecular, and comorbidity effects. Furthermore, changes in lean mass may not always reflect changes in muscle mass as the former measure includes not only muscle but also organs, bone, fluids, and water in fat tissue. Based on contemporary evidence with the addition of magnetic resonance imaging-based studies, skeletal muscle changes with GLP-1RA treatments appear to be adaptive: reductions in muscle volume seem to be commensurate with what is expected given ageing, 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 severity of disease may influence the selection of appropriate candidates for these therapies due to risk of sarcopenia. To further improve muscle health during weight loss, several pharmacological treatments to maintain or improve muscle mass designed in combination with GLP-1-based therapies are under development. Future research on GLP-1-based and other therapies designed for weight loss should focus on more accurate and meaningful assessments of muscle mass, composition, as well as function, mobility or strength, to better define their impact on muscle health for the substantial number of patients who will likely be taking these medications well into the future.
胰高血糖素样肽-1 受体激动剂 (GLP-1RAs) 和双重胰高血糖素样肽-1 受体 (GLP-1R)/葡萄糖依赖性胰岛素促分泌肽受体激动剂引起的体重减轻正在接近手术所达到的程度。然而，随着体重减轻的增加，人们担心它会对肌肉量（质量）、健康和功能产生潜在的副作用。在临床试验中，基于 GLP-1 的治疗对瘦体重变化的影响存在异质性：在一些研究中，瘦体重的减少范围占总体重减轻的 40%至 60%，而其他研究则显示瘦体重的减少约为总体重减轻的 15%或更少。这种异质性有几个潜在的原因，包括人群、药物特异性/分子和合并症的影响。此外，瘦体重的变化并不总是反映肌肉质量的变化，因为前者的测量不仅包括肌肉，还包括器官、骨骼、液体和脂肪组织中的水分。基于当代证据和磁共振成像研究的补充，GLP-1RA 治疗引起的骨骼肌变化似乎是适应性的：肌肉体积的减少似乎与衰老、疾病状态和体重减轻所预期的情况相适应，而胰岛素敏感性的提高和肌肉脂肪浸润的改善可能有助于提高肌肉质量的适应过程，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，年龄较大和疾病严重程度等因素可能会影响这些治疗方法的合适候选者的选择。为了在减肥过程中进一步改善肌肉健康，正在开发几种与 GLP-1 为基础的治疗相结合的药物治疗方法，以维持或改善肌肉量。未来关于基于 GLP-1 的治疗和其他旨在减肥的治疗方法的研究应侧重于更准确和有意义的肌肉量、组成以及功能、移动性或力量评估，以便更好地定义它们对大量可能在未来很长一段时间内服用这些药物的患者的肌肉健康的影响。
