Department of Medicine, Section of Endocrinology, Diabetes, Nutrition and Weight Management, Boston University School of Medicine, 720 Harrison Avenue, 8th Floor, Suite 801, Boston, MA, 02118, USA.
Curr Obes Rep. 2018 Jun;7(2):147-161. doi: 10.1007/s13679-018-0300-4.
Obesity is a global health crisis with detrimental effects on all organ systems leading to worsening disease state and rising costs of care. Persons with obesity failing lifestyle therapies need to be escalated to appropriate pharmacological treatment modalities, medical devices, and/or bariatric surgery if criteria are met and more aggressive intervention is needed. The progression of severe obesity in the patient population coupled with related co-morbidities necessitates the development of novel therapies for the treatment of obesity. This development is preceded by increased understanding of the underpinnings of energy regulation and neurohormonal pathways involved in energy homeostasis.
Though there are approved anti-obesity drugs available in the USA, newer drugs are now in the pipeline for development given the urgent need. This review focuses on anti-obesity drugs in the pipeline including centrally acting agents (setmelanotide, neuropeptide Y antagonist [velneperit], zonisamide-bupropion [Empatic], cannabinoid type-1 receptor blockers), gut hormones and incretin targets (new glucagon-like-peptide-1 [GLP-1] analogues [semaglutide and oral equivalents], amylin mimetics [davalintide, dual amylin and calcitonin receptor agonists], dual action GLP-1/glucagon receptor agonists [oxyntomodulin], triple agonists [tri-agonist 1706], peptide YY, leptin analogues [combination pramlintide-metreleptin]), and other novel targets (methionine aminopeptidase 2 inhibitor [beloranib], lipase inhibitor [cetilistat], triple monoamine reuptake inhibitor [tesofensine], fibroblast growth factor 21), including anti-obesity vaccines (ghrelin, somatostatin, adenovirus36). With these new drugs in development, anti-obesity therapeutics have potential to vastly expand allowing better treatment options and personalized approach to obesity care.
目的综述：肥胖是一个全球性的健康危机，对所有器官系统都有不利影响，导致疾病恶化和医疗费用增加。如果符合条件且需要更积极的干预，生活方式治疗失败的肥胖患者需要升级为适当的药物治疗、医疗器械和/或减重手术。随着肥胖患者病情的严重程度不断发展，以及相关合并症的出现，需要开发新的肥胖治疗方法。这一发展是在对能量调节的基本原理和参与能量平衡的神经激素途径有了更深入的了解之后进行的。
最近的发现：尽管美国有批准的抗肥胖药物，但鉴于迫切需要，现在有更多新的药物正在开发中。这篇综述集中讨论了正在研发中的抗肥胖药物，包括中枢作用药物（黑素细胞刺激素受体激动剂[setmelanotide]、神经肽 Y 拮抗剂[velneperit]、佐米曲普坦-安非他酮[Empatic]、大麻素 1 型受体阻滞剂）、肠激素和肠促胰岛素靶点（新的胰高血糖素样肽-1[GLP-1]类似物[semaglutide 和口服等效物]、淀粉样肽类似物[达伐林肽、双重淀粉样肽和降钙素受体激动剂]、双重作用 GLP-1/胰高血糖素受体激动剂[oxyntomodulin]、三重激动剂[三重激动剂 1706]、肽 YY、瘦素类似物[组合普兰林肽-美替瑞林]）和其他新靶点（甲硫氨酸氨肽酶 2 抑制剂[beloranib]、脂肪酶抑制剂[cetilistat]、三重单胺再摄取抑制剂[tesofensine]、成纤维细胞生长因子 21），包括抗肥胖疫苗（ghrelin、生长抑素、腺病毒 36）。随着这些新药物的开发，抗肥胖治疗方法有潜力大大扩展，为肥胖治疗提供更好的治疗选择和个性化方法。
