Glucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity.
Glucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity.
复制标题
胰高血糖素样肽1在临床肥胖的病理生理学和药物疗法中。
DOI：
10.4239/wjd.v7.i20.572
复制
发表时间：
2016-12-15
影响因子：
4.2
通讯作者：
Korbonits M
中科院分区：
文献类型：
--
作者：
Anandhakrishnan A;Korbonits M
虽然临床肥胖的病理生理学无疑是多方面的，但几条临床证据暗示胰高血糖素样肽1（GLP-1）信号传导的重要功能作用。在正常体重和肥胖受试者中评估GLP-1应答的临床研究表明，体重增加可能诱导GLP-1信号传导功能缺陷，从而促进肥胖表型的维持。此外，遗传学研究表明，GLP-1信号传导改变可能是导致肥胖的风险因素。由于功能性GLP-1信号传导的减少似乎在临床肥胖中起作用，因此药理学补充似乎是临床实践中肥胖医学管理的有希望的目标。与安慰剂对照和目前许可的抗肥胖药物相比，高剂量（3 mg/d）的GLP-1类似物利拉鲁肽在肥胖个体中实现并维持更大的体重减轻方面显示出有希望的结果。如果临床实践中的长期数据支持当前可用的上级短期和长期减肥疗效的证据，GLP-1类似物通常耐受良好，则有望实现肥胖症的成功、可持续的医学管理，这仍然是一个未满足的临床需求。
Though the pathophysiology of clinical obesity is undoubtedly multifaceted, several lines of clinical evidence implicate an important functional role for glucagon-like peptide 1 (GLP-1) signalling. Clinical studies assessing GLP-1 responses in normal weight and obese subjects suggest that weight gain may induce functional deficits in GLP-1 signalling that facilitates maintenance of the obesity phenotype. In addition, genetic studies implicate a possible role for altered GLP-1 signalling as a risk factor towards the development of obesity. As reductions in functional GLP-1 signalling seem to play a role in clinical obesity, the pharmacological replenishment seems a promising target for the medical management of obesity in clinical practice. GLP-1 analogue liraglutide at a high dose (3 mg/d) has shown promising results in achieving and maintaining greater weight loss in obese individuals compared to placebo control, and currently licensed anti-obesity medications. Generally well tolerated, provided that longer-term data in clinical practice supports the currently available evidence of superior short- and long-term weight loss efficacy, GLP-1 analogues provide promise towards achieving the successful, sustainable medical management of obesity that remains as yet, an unmet clinical need.