Novograd Joel, Mullally Jaime, Frishman William H
From the New York Medical College (student) Valhalla, NY.
Department of Medicine, Division of Endocrinology, New York Medical College/Westchester Medical Center, Valhalla, NY.
Cardiol Rev. 2022;30(6):324-329. doi: 10.1097/CRD.0000000000000430. Epub 2022 Jan 21.
Obesity is a major public health issue with an increasing prevalence worldwide. Excess body fat is associated with various comorbidities, as well as increased overall mortality risk. The benefits of weight loss are evident by the reductions in morbidity and mortality. The foundation for most weight loss programs involves strict lifestyle modification, including dietary change and exercise. Unfortunately, many individuals struggle with weight loss and chronic weight management due to difficulty adhering to long-term lifestyle modification and the metabolic adaptations that promote weight regain. The use of adjunctive pharmacotherapy has been employed to help patients not only achieve greater weight loss than lifestyle modification alone but also to assist with long-term weight management. Historically, antiobesity drugs have produced only modest weight loss and required at least once daily administration. Glucagon-like peptide-1 (GLP-1), a hormone with significant effects on glycemic control and weight regulation, has been explored for use as adjunctive pharmacotherapy for weight loss. Semaglutide, a GLP-1 receptor agonist, was recently approved by the Food and Drug Administration for chronic weight management in adults with obesity or who are overweight. The approval came after the publication of the Semaglutide Treatment Effect in People with Obesity clinical trials. In these 68-week trials, semaglutide 2.4 mg was associated with significantly greater weight loss compared to placebo. Semaglutide differs from other GLP-1 receptor agonists by having a longer half-life and producing greater weight loss. This article provides an overview of the discovery and mechanism of action of semaglutide 2.4 mg, and the clinical trials that led to its approval.
肥胖是一个重大的公共卫生问题，在全球范围内患病率不断上升。体内脂肪过多与各种合并症以及总体死亡风险增加有关。体重减轻带来的发病率和死亡率降低证明了减肥的益处。大多数减肥计划的基础都包括严格的生活方式改变，包括饮食变化和运动。不幸的是，许多人在减肥和长期体重管理方面面临困难，原因是难以坚持长期的生活方式改变以及促进体重反弹的代谢适应。辅助药物治疗的使用有助于患者不仅比单纯的生活方式改变实现更大程度的体重减轻，还能辅助长期体重管理。从历史上看，减肥药仅能带来适度的体重减轻，且需要至少每日服用一次。胰高血糖素样肽-1（GLP-1）是一种对血糖控制和体重调节有显著影响的激素，已被探索用作减肥的辅助药物治疗。司美格鲁肽是一种GLP-1受体激动剂，最近被美国食品药品监督管理局批准用于肥胖或超重成人的慢性体重管理。这一批准是在司美格鲁肽治疗肥胖症患者的临床试验结果公布之后。在这些为期68周的试验中，与安慰剂相比，2.4毫克司美格鲁肽与显著更大程度的体重减轻相关。司美格鲁肽与其他GLP-1受体激动剂不同，它具有更长的半衰期，并能带来更大程度的体重减轻。本文概述了2.4毫克司美格鲁肽的发现、作用机制以及促成其获批的临床试验。
