Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Clin Pharmacol Ther. 2014 Jan;95(1):53-66. doi: 10.1038/clpt.2013.204. Epub 2013 Oct 8.
Obesity is a growing pandemic, and related health and economic costs are staggering. Pharmacotherapy, partnered with lifestyle modifications, forms the core of current strategies to reduce the burden of this disease and its sequelae. However, therapies targeting weight loss have a significant history of safety risks, including cardiovascular and psychiatric events. Here, evolving strategies for developing antiobesity therapies, including targets, mechanisms, and developmental status, are highlighted. Progress in this field is underscored by Belviq (lorcaserin) and Qsymia (phentermine/topiramate), the first agents in more than 10 years to achieve regulatory approval for chronic weight management in obese patients. On the horizon, novel insights into metabolism and energy homeostasis reveal guanosine 3',5'-cyclic monophosphate (cGMP) signaling circuits as emerging targets for antiobesity pharmacotherapy. These innovations in molecular discovery may elegantly align with practical off-the-shelf approaches, leveraging existing approved drugs that modulate cGMP levels for the management of obesity.
肥胖是一种日益严重的流行疾病,与之相关的健康和经济成本令人震惊。药物治疗与生活方式改变相结合,构成了当前减轻这种疾病及其后果负担的核心策略。然而,针对体重减轻的治疗方法存在重大的安全风险,包括心血管和精神事件。在这里,突出强调了开发抗肥胖治疗方法的不断发展的策略,包括靶点、机制和发展状况。Belviq(lorcaserin)和 Qsymia(phentermine/topiramate)的进展强调了这一领域的进展,这是 10 多年来第一种获得肥胖患者慢性体重管理监管批准的药物。在不远的将来,对新陈代谢和能量稳态的新见解揭示了环鸟苷酸 3',5'-环单磷酸(cGMP)信号通路作为抗肥胖药物治疗的新兴靶点。这些分子发现方面的创新可能会巧妙地与现成的实用方法相结合,利用现有的调节 cGMP 水平以治疗肥胖症的已批准药物。