Cosentino Gina, Conrad Ariane O, Uwaifo Gabriel I
Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
Drug Des Devel Ther. 2011 Apr 5;7:267-78. doi: 10.2147/DDDT.S31443. Print 2013.
Obesity is now a major public health concern worldwide with increasing prevalence and a growing list of comorbidities and complications. The morbidity, mortality and reduced productivity associated with obesity and its complications result in a major burden to health care costs. Obesity is a complex chronic medical syndrome often with multiple different etiologic factors in individual patients. The long term successful management of obesity remains particularly challenging and invariably requires a multifaceted approach including lifestyle and behavioral modification, increased physical activity, and adjunctive pharmacotherapy. Bariatric surgery remains a last resort though at present it has the best results for achieving sustained robust weight loss. Obesity pharmacotherapy has been very limited in its role for long term obesity management because of the past history of several failed agents as well as the fact that presently available agents are few, and generally utilized as monotherapy. The recent FDA approval of the fixed drug combination of phentermine and extended release topiramate (topiramate-ER) (trade name Qsymia™) marks the first FDA approved combination pharmacotherapeutic agent for obesity since the Phen-Fen combination of the 1990s. This review details the history and clinical trial basis for the use of both phentermine and topiramate in obesity therapeutics as well as the results of clinical trials of their combination for obesity treatment in humans. The initial clinical approval trials offer evidence that this fixed drug combination offers synergistic potential for effective, robust and sustained weight loss with mean weight loss of at least 10% of baseline achieved and sustained for up to 2 years in over 50% of subjects treated. It is anticipated that this agent will be the first in a new trend of multi-agent combination therapy for the chronic adjunctive management of obesity.
肥胖现已成为全球主要的公共卫生问题，其患病率不断上升，合并症和并发症的种类也日益增多。与肥胖及其并发症相关的发病率、死亡率和生产力下降给医疗成本带来了巨大负担。肥胖是一种复杂的慢性医学综合征，个体患者通常存在多种不同的病因。肥胖的长期成功管理仍然极具挑战性，始终需要多方面的方法，包括生活方式和行为改变、增加体育活动以及辅助药物治疗。减肥手术仍是最后的手段，不过目前它在实现持续显著体重减轻方面效果最佳。由于过去几种药物研发失败，以及目前可用药物数量稀少且一般用作单一疗法，肥胖药物治疗在长期肥胖管理中的作用一直非常有限。美国食品药品监督管理局（FDA）最近批准了苯丁胺与缓释托吡酯（托吡酯-ER）的固定药物组合（商品名Qsymia™），这标志着自20世纪90年代的芬氟拉明-苯丙胺组合以来，首个获得FDA批准的用于肥胖治疗的组合药物治疗剂。本综述详细介绍了苯丁胺和托吡酯在肥胖治疗中的使用历史和临床试验依据，以及它们联合用于人类肥胖治疗的临床试验结果。最初的临床批准试验提供了证据，表明这种固定药物组合具有协同潜力，可实现有效、显著和持续的体重减轻，在超过50%接受治疗的受试者中，平均体重减轻至少达到基线的10%，并持续长达2年。预计该药物将成为肥胖慢性辅助管理多药联合治疗新趋势中的首个药物。
