Pennington Biomedical Research Center, Baton Rouge, LA, USA.
Handb Exp Pharmacol. 2022;274:387-414. doi: 10.1007/164_2021_560.
Older medications approved for chronic weight management (orlistat, naltrexone/bupropion, liraglutide 3 mg and, in the USA, phentermine/topiramate) have not been widely adopted by health care providers. Those medications produce only modest additional weight loss when used to augment lifestyle intervention. However, semaglutide 2.4 mg weekly has recently emerged and produces much more weight loss - on average 15% weight loss at 1 year. Semaglutide's enhanced efficacy and that its class (GLP-1 receptor analogs) is well-known may result in more clinicians adopting pharmacotherapy. Furthermore, the first dedicated cardiovascular outcome trial powered for superiority testing an anti-obesity medication (SELECT) is underway with semaglutide 2.4 mg. A positive outcome will further promote the concept that weight management should be a primary target for cardiometabolic disease control. In phase 3, tirzepatide and cagrilintide/semaglutide combination are showing promise for even greater weight loss efficacy. Another recently approved medication takes a personalized medicine approach; setmelanotide is approved as a therapy for those with some of the ultra-rare genetic diseases characterized by severe, early onset obesity. This chapter reviews the currently available and anticipated medications for chronic weight management as well as those approved for the genetic and syndromic obesities.
已批准用于慢性体重管理的较老药物(奥利司他、纳曲酮/安非他酮、利拉鲁肽 3mg,以及在美国批准的苯丁胺/托吡酯)并未被医疗保健提供者广泛采用。当这些药物被用于辅助生活方式干预时,只能产生适度的额外体重减轻。然而,每周注射 2.4mg 的司美格鲁肽最近出现,并且能产生更多的体重减轻——平均在 1 年内减轻 15%的体重。司美格鲁肽增强的疗效及其所属类别(GLP-1 受体激动剂)众所周知,可能会导致更多的临床医生采用药物治疗。此外,第一个专门针对心血管结局的、具有优势测试能力的抗肥胖药物试验(SELECT)正在进行中,使用的是司美格鲁肽 2.4mg。阳性结果将进一步促进这样一种观念,即体重管理应该是控制心脏代谢疾病的主要目标。在第 3 阶段,替西帕肽和卡格列净/司美格鲁肽联合用药在体重减轻疗效方面显示出更大的潜力。另一种最近批准的药物采用了个性化药物方法;setmelanotide 被批准用于治疗那些具有某些极罕见的遗传疾病的患者,这些疾病的特征是严重的、早期发病的肥胖。本章回顾了目前可用于慢性体重管理的药物以及那些批准用于遗传性和综合征性肥胖的药物。