Novograd Joel, Mullally Jamie A, Frishman William H
From the New York Medical College, Valhalla, NY.
Department of Medicine, New York Medical College, Valhalla, NY.
Cardiol Rev. 2023;31(5):278-283. doi: 10.1097/CRD.0000000000000515. Epub 2023 Mar 8.
The worldwide prevalence of obesity has been increasing progressively over the past few decades and is predicted to continue to rise in coming years. Unfortunately, this epidemic is also affecting increasing rates of children and adolescents, posing a serious global health concern. Increased adiposity is associated with various comorbidities and increased mortality risk. Conversely, weight loss and chronic weight management are associated with improvements in overall morbidity and mortality. The pathophysiology of obesity is multifactorial with complex interactions between genetic and environmental factors. The foundation of most weight loss plans is lifestyle modification including dietary change and exercise. However, lifestyle modification alone is often insufficient to achieve clinically meaningful weight loss due to physiological mechanisms that limit weight reduction and promote weight regain. Therefore, research has focused on adjunctive pharmacotherapy to enable patients to achieve greater weight loss and improved chronic weight maintenance compared to lifestyle modification alone. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin hormone analogs that have proven effective for the management of type 2 diabetes mellitus as well as obesity and overweight. Tirzepatide is a novel "twincretin" that functions as a dual glucose-dependent insulinotropic polypeptide and GLP-1 RA. Tirzepatide was recently approved by the Food and Drug Administration for the management of type 2 diabetes. Similar to previously approved GLP-1RAs, weight loss is a common side effect of tirzepatide which prompted research focused on its use as a primary weight loss therapy. Although this drug has not yet been approved as an antiobesity medication, there are several phase 3 clinical trials that have demonstrated superior weight loss efficacy compared with previously approved medications. This review article will discuss the discovery and mechanism of tirzepatide, as well as the completed and ongoing trials that may lead to its approval as an adjunctive pharmacotherapy for weight loss.
在过去几十年中，全球肥胖症患病率一直在逐步上升，预计未来几年还将继续攀升。不幸的是，这一流行病在儿童和青少年中的发病率也在不断上升，成为全球严重的健康问题。肥胖程度增加与多种合并症及死亡风险增加相关。相反，体重减轻和慢性体重管理则与总体发病率和死亡率的改善有关。肥胖的病理生理学是多因素的，遗传和环境因素之间存在复杂的相互作用。大多数减肥计划的基础是生活方式的改变，包括饮食变化和运动。然而，由于生理机制限制体重减轻并促进体重反弹，仅靠生活方式的改变往往不足以实现具有临床意义的体重减轻。因此，研究集中在辅助药物治疗上，以使患者与仅进行生活方式改变相比能够实现更大程度的体重减轻并改善慢性体重维持。胰高血糖素样肽-1受体激动剂（GLP-1RAs）是肠促胰岛素激素类似物，已被证明对2型糖尿病以及肥胖和超重的管理有效。替尔泊肽是一种新型的“双肠促胰岛素”，具有葡萄糖依赖性促胰岛素多肽和GLP-1 RA的双重功能。替尔泊肽最近被美国食品药品监督管理局批准用于治疗2型糖尿病。与先前批准的GLP-1RAs类似，体重减轻是替尔泊肽的常见副作用，这促使人们研究将其用作主要的减肥疗法。尽管这种药物尚未被批准为抗肥胖药物，但有几项3期临床试验表明，其减肥效果优于先前批准的药物。这篇综述文章将讨论替尔泊肽的发现和作用机制，以及可能导致其被批准作为减肥辅助药物治疗的已完成和正在进行的试验。
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