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胰高血糖素样肽1在临床肥胖症的病理生理学及药物治疗中的作用

Glucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity.

作者信息

Anandhakrishnan Ananthi, Korbonits Márta

机构信息

Ananthi Anandhakrishnan, Márta Korbonits, Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6 BQ, United Kingdom.

出版信息

World J Diabetes. 2016 Dec 15;7(20):572-598. doi: 10.4239/wjd.v7.i20.572.

DOI:10.4239/wjd.v7.i20.572
PMID:28031776
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5155232/
Abstract

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.

摘要

尽管临床肥胖的病理生理学无疑是多方面的，但几条临床证据表明胰高血糖素样肽1（GLP-1）信号传导具有重要的功能作用。评估正常体重和肥胖受试者中GLP-1反应的临床研究表明，体重增加可能会导致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信号改变可能是肥胖发生的一个危险因素。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，因此药物补充似乎是临床实践中肥胖医学管理的一个有前景的靶点。与安慰剂对照和目前已获批的抗肥胖药物相比，高剂量（3 mg/d）的GLP-1类似物利拉鲁肽在肥胖个体实现并维持更大程度的体重减轻方面已显示出有前景的结果。一般耐受性良好，前提是临床实践中的长期数据支持目前关于短期和长期体重减轻疗效更佳的现有证据，GLP-1类似物有望实现对肥胖的成功、可持续医学管理，而这仍是尚未满足的临床需求。

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