Purpose of Review

Obesity affects over than 600 million adults worldwide resulting in multi-organ complications and major socioeconomic impact. The purpose of this review is to summarise the physiological effects as well as the therapeutic implications of the gut hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin, peptide YY (PYY), and glucose-dependent insulinotropic peptide (GIP) in the treatment of obesity and type 2 diabetes.

Recent Findings

Clinical trials have proven that the widely used GLP-1 analogues have pleotropic effects beyond those on weight and glucose metabolism and appear to confer favourable cardiovascular and renal outcomes. However, GLP-1 analogues alone do not deliver sufficient efficacy for the treatment of obesity, being limited by their dose-dependent gastrointestinal side effects. Novel dual agonists for GLP-1/glucagon and GLP-1/GIP are being developed by the pharmaceutical industry and have demonstrated some promising results for weight loss and improvement in glycaemia over and above GLP-1 analogues. Triagonists (for example GLP-1/GIP/glucagon) are currently in pre-clinical or early clinical development.

Summary

Gastrointestinal hormones possess complementary effects on appetite, energy expenditure, and glucose metabolism. We highlight the idea that combinations of these hormones may represent the way forward in obesity and diabetes therapeutics.

中文翻译：

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胃肠道肽作为减轻肥胖和代谢综合征的治疗靶标。

审查目的

肥胖症影响全世界超过6亿成年人，导致多器官并发症和重大的社会经济影响。这篇综述的目的是总结肠道激素胰高血糖素样肽-1（GLP-1），胃泌素调节素，YY肽（PYY）和葡萄糖依赖性促胰岛素肽（GIP）的生理效应及其治疗意义。在肥胖和2型糖尿病的治疗中。

最近的发现

临床试验已经证明，广泛使用的GLP-1类似物对体重和葡萄糖代谢的影响远非多效性，并且似乎具有良好的心血管和肾脏预后。然而，仅GLP-1类似物不能提供足够的治疗肥胖的功效，这受到其剂量依赖性胃肠道副作用的限制。制药业正在开发针对GLP-1 /胰高血糖素和GLP-1 / GIP的新型双重激动剂，并已证明与GLP-1类似物相比，减肥和改善血糖的效果令人鼓舞。三效激动剂（例如GLP-1 / GIP /胰高血糖素）目前处于临床前或早期临床开发中。

概要

胃肠激素对食欲，能量消耗和葡萄糖代谢具有互补作用。我们强调这些激素的组合可能代表肥胖和糖尿病治疗方法的前进方向。