背景:肥胖已达到流行病的程度,超过40%的美国人口受到影响。尽管传统上是通过改变生活方式来管理的,减肥疗法的频率较低,有显著的药理学进步。
目的:对体重增加和肥胖的神经激素和生理理解进行叙述性回顾,和发展,临床试验,适应症,预期临床结果,以及当前FDA批准和即将上市的抗肥胖药物(AOM)的相关风险。
方法:我们在PubMed中对肥胖的病理生理学和并发症的文章进行了全面综述,包括术语“神经激素”,\'肥胖\',\'递增\',和“减肥”。接下来,我们搜索了所有FDA批准的AOM的临床试验数据,包括orlistat的通用名和商标名,苯丁胺/托吡酯,安非他酮/纳曲酮,利拉鲁肽,还有semaglutide.进行了额外的搜索,以寻找替拉帕肽和retatrutide-药物,期待监管部门的批准。搜索包括与作用机制相关的术语组合,适应症,副作用,风险,和未来的方向。
结果:我们回顾了肥胖的病理生理学,包括肠促胰岛素和胰高血糖素的具体作用。提供了支持使用各种FDA批准的减肥药物的临床数据,包括安慰剂对照或,当可用时,正面交锋的试验.有益的代谢作用,包括对肝脏疾病的影响,讨论了药物的不良反应和风险,包括胃肠蠕动改变和围手术期抽吸的风险。
结论:AOMs已经确定了减肥的功效和有效性,甚至超过52周。进一步的药理学选择,例如双重和三重增量,可能是即将加入的临床实践,以对抗肥胖及其代谢后果,如代谢功能障碍相关的脂肪变性肝病。
Obesity has reached epidemic proportions, with >40% of the US population affected. Although traditionally managed by lifestyle modification, and less frequently by bariatric therapies, there are significant pharmacological advancements.
To conduct a narrative
review of the neurohormonal and physiological understanding of weight gain and obesity, and the development, clinical testing, indications, expected clinical outcomes, and associated risks of current FDA-approved and upcoming anti-obesity medications (AOMs).
We conducted a comprehensive
review in PubMed for articles on pathophysiology and complications of obesity, including terms \'neurohormonal\', \'obesity\', \'incretin\', and \'weight loss\'. Next, we searched for clinical trial data of all FDA-approved AOMs, including both the generic and trade names of orlistat, phentermine/topiramate, bupropion/naltrexone, liraglutide, and semaglutide. Additional searches were conducted for tirzepatide and retatrutide - medications expecting regulatory approval. Searches included combinations of terms related to mechanism of action, indications, side effects, risks, and future directions.
We reviewed the pathophysiology of obesity, including specific role of incretins and glucagon. Clinical data supporting the use of various FDA-approved medications for weight loss are presented, including placebo-controlled or, when available, head-to-head trials. Beneficial metabolic effects, including impact on liver disease, adverse effects and risks of medications are discussed, including altered gastrointestinal motility and risk for periprocedural aspiration.
AOMs have established efficacy and effectiveness for weight loss even beyond 52 weeks. Further pharmacological options, such as dual and triple incretins, are probable forthcoming additions to clinical practice for combating obesity and its metabolic consequences such as metabolic dysfunction-associated steatotic liver disease.