The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update.

IF 3.9 3区医学 Q2 ENDOCRINOLOGY & METABOLISM Endocrinology and Metabolism Pub Date : 2024-02-01 Epub Date: 2024-02-14 DOI:10.3803/EnM.2024.1942

Agnieszka Jakubowska, Carel W le Roux, Adie Viljoen

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Abstract

Obesity is the fifth leading risk factor for global deaths with numbers continuing to increase worldwide. In the last 20 years, the emergence of pharmacological treatments for obesity based on gastrointestinal hormones has transformed the therapeutic landscape. The successful development of glucagon-like peptide-1 (GLP-1) receptor agonists, followed by the synergistic combined effect of glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists achieved remarkable weight loss and glycemic control in those with the diseases of obesity and type 2 diabetes. The multiple cardiometabolic benefits include improving glycemic control, lipid profiles, blood pressure, inflammation, and hepatic steatosis. The 2023 phase 2 double-blind, randomized controlled trial evaluating a GLP-1/GIP/glucagon receptor triagonist (retatrutide) in patients with the disease of obesity reported 24.2% weight loss at 48 weeks with 12 mg retatrutide. This review evaluates the current available evidence for GLP-1 receptor agonists, dual GLP-1/GIP receptor co-agonists with a focus on GLP-1/GIP/glucagon receptor triagonists and discusses the potential future benefits and research directions.

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通往三重激动剂之路：胰高血糖素样肽 1、葡萄糖依赖性促胰岛素多肽和胰高血糖素受体--最新进展。

肥胖症是导致全球死亡的第五大风险因素，而且这一数字在全球范围内持续增长。在过去的 20 年里，基于胃肠激素的肥胖症药物疗法的出现改变了治疗格局。胰高血糖素样肽-1（GLP-1）受体激动剂的成功开发，以及葡萄糖依赖性促胰岛素多肽（GIP）/GLP-1受体激动剂的协同作用，使肥胖症和 2 型糖尿病患者的体重明显减轻，血糖得到有效控制。其多重心脏代谢益处包括改善血糖控制、血脂状况、血压、炎症和肝脂肪变性。2023 期双盲随机对照试验评估了 GLP-1/GIP/ 胰高血糖素受体三拮抗剂（雷他曲肽）对肥胖症患者的治疗效果，结果显示，服用 12 毫克雷他曲肽 48 周后，体重减轻了 24.2%。本综述评估了 GLP-1 受体激动剂、GLP-1/GIP 双受体共拮抗剂（重点是 GLP-1/GIP/ 胰高血糖素受体三拮抗剂）的现有证据，并讨论了未来的潜在益处和研究方向。

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来源期刊

Endocrinology and Metabolism Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

6.60

自引率

5.90%

发文量

145

审稿时长

24 weeks

期刊介绍： The aim of this journal is to set high standards of medical care by providing a forum for discussion for basic, clinical, and translational researchers and clinicians on new findings in the fields of endocrinology and metabolism. Endocrinology and Metabolism reports new findings and developments in all aspects of endocrinology and metabolism. The topics covered by this journal include bone and mineral metabolism, cytokines, developmental endocrinology, diagnostic endocrinology, endocrine research, dyslipidemia, endocrine regulation, genetic endocrinology, growth factors, hormone receptors, hormone action and regulation, management of endocrine diseases, clinical trials, epidemiology, molecular endocrinology, neuroendocrinology, neuropeptides, neurotransmitters, obesity, pediatric endocrinology, reproductive endocrinology, signal transduction, the anatomy and physiology of endocrine organs (i.e., the pituitary, thyroid, parathyroid, and adrenal glands, and the gonads), and endocrine diseases (diabetes, nutrition, osteoporosis, etc.).