Comparing the anorexigenic effects and mechanisms of gut-derived GLP-1 and its receptor agonists: insights into incretin-based therapies for obesity.

IF 1.2 Q4 ENDOCRINOLOGY & METABOLISM

Diabetology International Pub Date : 2025-05-20 eCollection Date: 2025-07-01 DOI:10.1007/s13340-025-00819-9

Yuta Masuda, Kento Ohbayashi, Yusaku Iwasaki

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引用次数: 0

Abstract

Obesity continues to increase worldwide. The primary cause of obesity is overeating, but the development of pharmacological treatments for obesity related to overeating has taken longer than expected. Recently, agonists of glucagon-like peptide-1 (GLP-1) receptor, designed based on the gut hormone GLP-1, have been developed as anti-obesity drugs and have demonstrated remarkable efficacy in treating both obesity and diabetes. Meanwhile, recent research using factors that promote GLP-1 secretion has highlighted the significance of endogenous GLP-1 function. This review provides an overview of the anorexigenic effects, adverse effects, and their underlying mechanisms of GLP-1 receptor agonists and endogenous gut-derived GLP-1. Furthermore, it discusses the potential anti-obesity effects of dual agonists targeting both the glucose-dependent insulinotropic polypeptide (GIP) receptor and the GLP-1 receptor, which have gained attention in recent years. Finally, we compare the beneficial effects of GLP-1 receptor agonists and meal-induced gut GLP-1 secretion on overeating-induced obesity and discuss how combining these approaches may complement each other's limitations and serve as a promising long-term strategy for preventing and treating obesity.

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比较肠源性GLP-1及其受体激动剂的厌氧性作用和机制：对基于肠促胰岛素的肥胖治疗的见解。

肥胖症在世界范围内持续增加。肥胖的主要原因是暴饮暴食，但与暴饮暴食有关的肥胖的药物治疗的发展比预期的要长。近年来，以肠道激素GLP-1为基础设计的胰高血糖素样肽-1 （glucagon-like peptide-1, GLP-1）受体激动剂（agonists of glucagon-like peptide-1, GLP-1）受体激动剂被开发为抗肥胖药物，在治疗肥胖和糖尿病方面均有显著疗效。同时，近年来利用促进GLP-1分泌因子的研究也强调了内源性GLP-1功能的重要性。本文综述了GLP-1受体激动剂和内源性肠源性GLP-1的厌氧性作用、不良反应及其潜在机制。此外，本文还讨论了近年来备受关注的针对葡萄糖依赖性胰岛素性多肽（GIP）受体和GLP-1受体的双重激动剂的潜在抗肥胖作用。最后，我们比较了GLP-1受体激动剂和膳食诱导的肠道GLP-1分泌对暴饮暴食引起的肥胖的有益作用，并讨论了如何将这些方法结合起来，以补充彼此的局限性，并作为预防和治疗肥胖的有希望的长期策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetology International ENDOCRINOLOGY & METABOLISM-

CiteScore

3.90

自引率

4.50%

发文量

期刊介绍： Diabetology International, the official journal of the Japan Diabetes Society, publishes original research articles about experimental research and clinical studies in diabetes and related areas. The journal also presents editorials, reviews, commentaries, reports of expert committees, and case reports on any aspect of diabetes. Diabetology International welcomes submissions from researchers, clinicians, and health professionals throughout the world who are interested in research, treatment, and care of patients with diabetes. All manuscripts are peer-reviewed to assure that high-quality information in the field of diabetes is made available to readers. Manuscripts are reviewed with due respect for the author''s confidentiality. At the same time, reviewers also have rights to confidentiality, which are respected by the editors. The journal follows a single-blind review procedure, where the reviewers are aware of the names and affiliations of the authors, but the reviewer reports provided to authors are anonymous. Single-blind peer review is the traditional model of peer review that many reviewers are comfortable with, and it facilitates a dispassionate critique of a manuscript.