Ryan Donna H
Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA, 70808, USA.
, New Orleans, USA.
Rev Endocr Metab Disord. 2025 May 5. doi: 10.1007/s11154-025-09967-4.
The development of drugs targeting Nutrient Stimulated Hormone receptors has ushered in a dramatic change in our approach to weight management because of their ability to achieve weight losses of 10%, 20%, even 30% in significant numbers of patients. Additionally, disease modifying properties of these medications are compelling. Indications now include cardiovascular risk reduction, obstructive sleep apnea and diabetes management, and emerging evidence supports efficacy for heart failure and chronic kidney disease. These medications would need to be taken long term and the population being treated will be older than the traditional weight management patient. Emerging evidence cautions that the loss of excessive lean mass with some of the newer medications may be problematic. This is not a concern for most patients who will need the medications, but it is a concern in an older population, since loss of muscle and bone accelerates and progresses past age 60. Of weight lost with semaglutide, approximately 45% is from lean mass, while with tirzepatide, it is 25%. Going forward, combining another NuSH such as glucagon or amylin with the GLP-1 receptor agonists may lessen loss of lean mass. Another approach under study is the use of MAPi - myostatin-activin pathway inhibitors. Promising results with bimagrumab are spurring investigaton in this area. For the full potential of disease modification to be achieved, it's a given that we must demonstrate safe, long term body composition improvement when the new medications are deployed, especially in the older population. This narrative review discusses the justification for focus on lean mass preservation and reviews the status of relevant drugs in development.
靶向营养刺激激素受体的药物的研发给我们的体重管理方法带来了巨大变化，因为它们能够使大量患者体重减轻10%、20%甚至30%。此外，这些药物的疾病修饰特性也很引人注目。目前的适应症包括降低心血管风险、治疗阻塞性睡眠呼吸暂停和糖尿病，并且新出现的证据支持其对心力衰竭和慢性肾病也有效。这些药物需要长期服用，而且接受治疗的人群将比传统体重管理患者的年龄更大。新出现的证据警示，一些新型药物导致过多瘦体重流失可能会有问题。这对大多数需要这些药物的患者来说并非问题，但对于老年人群体却是一个担忧，因为肌肉和骨骼流失在60岁以后会加速且加剧。使用司美格鲁肽减重时，约45%的体重减轻来自瘦体重，而替尔泊肽则为25%。展望未来，将另一种营养刺激激素（如胰高血糖素或胰淀素）与GLP - 1受体激动剂联合使用可能会减少瘦体重的流失。正在研究的另一种方法是使用MAPi——肌生成抑制素 - 激活素信号通路抑制剂。比马鲁单抗取得的有前景的结果正在推动该领域的研究。为了充分发挥疾病修饰的潜力，当使用这些新药时，尤其是在老年人群体中，我们必须证明其能安全、长期地改善身体成分，这是不言而喻的。这篇叙述性综述讨论了关注保留瘦体重的理由，并回顾了相关在研药物的现状。
