Emerging opportunities for the treatment of metabolic diseases: Glucagon-like peptide-1 based multi-agonists
Emerging opportunities for the treatment of metabolic diseases: Glucagon-like peptide-1 based multi-agonists
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DOI：
10.1016/j.mce.2015.07.003
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发表时间：
2015-12-15
影响因子：
4.1
通讯作者：
Mueller, Timo D.
中科院分区：
文献类型：
--
作者：
Finan, Brian;Clemmensen, Christoffer;Mueller, Timo D.
肥胖是代谢综合征及其并发症的致病途径，因此，旨在预防或逆转肥胖背后的代谢紊乱的干预措施具有巨大的治疗前景。然而，能量平衡调节的复杂性，加上人类肥胖的异质性病理生理学，使得有效的药物干预变得非常困难。事实上，在减肥药物中寻找银弹的过程中，充斥着疗效平平、副作用不可接受的药物。这在一定程度上可能是因为许多药物干预在历史上都是针对单一分子靶标的。新的多分子联合疗法在减肥方面显示出有希望的临床结果，但多功能单分子疗法可能比辅助联合疗法提供更多的优势。参与新陈代谢生理控制的多种激素所产生的具有综合活性的单分子已成为逆转肥胖的更有前途的候选分子之一。胰升糖素样肽-1(GLP-1)是这些单分子多激动剂中的一个统一因素。这篇综述的范围是总结基于GLP-1的治疗的临床前和临床现状，重点是组合治疗，特别强调显示多激动剂特性的单分子化合物。(C)2015爱思唯尔爱尔兰有限公司。保留所有权利。
Obesity is a pathogenic gateway to the metabolic syndrome and the complications thereof, thus interventions aimed at preventing or reversing the metabolic derangements underlying obesity hold great therapeutic promise. However, the complexity of energy balance regulation, combined with the heterologous pathophysiology of human obesity, renders effective medicinal intervention very difficult. Indeed, the search for the silver bullet in anti-obesity medicines has been laden with drugs of under-whelming efficacy and unacceptable side effects. This can partly be the consequence that many of these drug interventions have been historically directed at single molecular targets. New multi-molecular combination therapies have shown promising clinical outcomes in terms of weight loss, yet multifunctional single molecules may offer even more advantages than adjunctive co-treatments. Single molecules with integrated activities derived from multiple hormones involved in the physiological control of metabolism have emerged as one of the more promising candidates for reversing obesity. The inclusion of glucagon-like peptide-1 (GLP-1) as one of the constituents is a unifying factor amongst the majority of these unimolecular multi-agonists. The scope of this review is to summarize the current preclinical and clinical landscape of GLP-1-based therapies, focusing on combinatorial therapies with a particular emphasis on single molecule compounds displaying multi-agonist properties. (C) 2015 Elsevier Ireland Ltd. All rights reserved.