Valsamakis G, Lois K, Kumar S, Mastorakos G
Endocrine Unit, 2nd Department of Obs and Gynae, Areteeion University Hospital, Athens Medical School National and Kapodistrian University of Athens, Athens, Greece; WISDEM Centre for Diabetes, Endocrinology and Metabolism, Warwick Medical School, University of Warwick, Coventry, UK.
Clin Obes. 2014 Aug;4(4):209-19. doi: 10.1111/cob.12064. Epub 2014 Jun 23.
The pharmacotherapy of obesity has historically recorded an overall poor safety and efficacy profile largely because of the complex mechanisms involved in the pathophysiology of obesity. It is hoped that a better understanding of the regulation of body weight will lead us to the development of effective and safer drugs. Recent advances in our understanding of the regulation of energy homeostasis has allowed the design of novel anti-obesity drugs targeting specific molecules crucial for the modulation of energy balance, including drugs that induce satiety, modulate nutrient absorption or influence metabolism or lipogenesis. Almost a decade after the Food and Drug Administration approved the first weight loss medication, it recently approved two novel anti-obesity drugs Belviq (lorcaserin) and Qsymia (topiramate and phentermine), thus signalling the beginning of a new era in the pharmacotherapy of obesity. It is believed that the next generation of weight-loss drugs will be based on combination treatments with gut hormones in a manner that mimics the changes underlying surgically induced weight loss thus introducing the so called 'bariatric pharmacotherapy'. An in-depth understanding of the interrelated physiological and behavioural effects of these new molecules together with the development of new treatment paradigms is needed so that future disappointments in the field of obesity pharmacotherapy may be avoided.
肥胖症的药物治疗在历史上总体安全性和有效性记录不佳，这主要是因为肥胖症病理生理学涉及复杂机制。人们希望，对体重调节有更深入的了解将引领我们研发出更有效、更安全的药物。最近，我们对能量稳态调节的理解取得进展，这使得能够设计出新型抗肥胖药物，这些药物靶向对调节能量平衡至关重要的特定分子，包括诱导饱腹感、调节营养吸收或影响代谢或脂肪生成的药物。美国食品药品监督管理局批准首款减肥药物近十年后，最近又批准了两种新型抗肥胖药物——Belviq（氯卡色林）和Qsymia（托吡酯和苯丁胺），这标志着肥胖症药物治疗新时代的开始。人们认为，下一代减肥药物将基于与肠道激素的联合治疗，其方式模仿手术诱导体重减轻的潜在变化，从而引入所谓的“减肥药物疗法”。需要深入了解这些新分子的相关生理和行为效应，并开发新的治疗模式，以便避免肥胖症药物治疗领域未来出现令人失望的情况。
