New Amylin-Based Agonists for the Treatment of Obesity and Type 2 Diabetes Mellitus.

IF 4.2 3区医学 Q2 Medicine

Diabetes Therapy Pub Date : 2026-09-28 DOI:10.1007/s13300-026-01921-0

Theodoros Panou, Evanthia Gouveri, Djordje S Popovic, Nikolaos Papanas

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引用次数: 0

Abstract

Introduction: Type 2 diabetes mellitus (T2DM) and obesity represent two major global health challenges. Amylin-based agonists offer a promising perspective. Three frontrunner agents of this class are increasingly being investigated: zenagamtide, eloralintide and cagrilintide-semaglutide (CagriSema).

Methods: A search in PubMed/MEDLINE, Scopus and Google Scholar was conducted with the use of appropriate keywords until June 2026 for this narrative review.

Results: Zenagamtide (formerly known as amycretin), a unimolecular long-lasting amylin and glucagon-like peptide-1 receptor (GLP-1R) co-agonist, achieved weight loss up to 13.1% (phase 1 study, 85 days) in obesity trials as an oral formulation and up to 24.3% (phase 1b/2a study, 36 weeks) as a subcutaneous formulation. Moreover, eloralintide, a long-acting mostly amylin type 1 receptor (AMY1R) agonist, achieved weight loss up to 20.1% (phase 2 study, 48 weeks), and CagriSema resulted in weight loss up to 22.7% (phase 3a study, 68 weeks). All these agents reduced body mass index (BMI) and waist circumference (WC). In T2DM, CagriSema reduced glycated haemoglobin (HbA_1c) by up to 2.0% (trial product estimand, phase 3a study, 68 weeks) and is currently the most well-studied agent in T2DM. In treatment-naïve people with T2DM, this agent has been successfully used, leading even to T2DM remission in approximately one out of two CagriSema users (phase 3a, 40 weeks). In individuals with T2DM receiving basal insulin, it reduced insulin dose by 20 units compared with the control arm (phase 3a, 40 weeks). The safety profile of amycretin and CagriSema is overall consistent with that of glucagon-like peptide 1 receptor agonists (GLP-1RAs). Preliminary evidence suggests that eloralintide, as an AMY1R monoagonist, was associated with a distinct adverse events profile, including fatigue, headache and appetite loss.

Conclusions: These agents hold therapeutic potential in the management of both T2DM and obesity, as shown by preliminary clinical trial outcomes. Further trials are now needed to validate them in clinical practice.

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治疗肥胖和2型糖尿病的新型胰淀素激动剂。

2型糖尿病（T2DM）和肥胖是全球两大健康挑战。以胰肽为基础的激动剂提供了一个有希望的前景。这类药物中有三种领先的药物正在被越来越多地研究：zenagamtide， eloralintide和cagrilintide-semaglutide （CagriSema）。方法：检索PubMed/MEDLINE、Scopus和谷歌Scholar，使用合适的关键词进行检索，直至2026年6月。结果：Zenagamtide（以前称为amycretin）是一种单分子长效胰高血糖素和胰高血糖素样肽-1受体（GLP-1R）共激动剂，在肥胖试验中口服制剂的体重减轻率高达13.1%（一期研究，85天），皮下制剂的体重减轻率高达24.3% （1b/2a期研究，36周）。此外，eloralintide是一种长效的AMY1R受体激动剂，体重减轻高达20.1%（2期研究，48周），CagriSema的体重减轻高达22.7% （3a期研究，68周）。所有这些药物都能降低体重指数（BMI）和腰围（WC）。在T2DM中，CagriSema将糖化血红蛋白（HbA1c）降低了2.0%（试验产品估计，3a期研究，68周），是目前研究最充分的T2DM药物。在treatment-naïve T2DM患者中，该药物已成功使用，甚至导致大约1 / 2的CagriSema患者T2DM缓解（3a期，40周）。在接受基础胰岛素治疗的T2DM患者中，与对照组相比，胰岛素剂量减少了20个单位（3a期，40周）。amycretin和CagriSema的安全性总体上与胰高血糖素样肽1受体激动剂（GLP-1RAs）一致。初步证据表明，作为一种AMY1R单受体激动剂，依洛林肽与明显的不良事件相关，包括疲劳、头痛和食欲减退。结论：初步临床试验结果显示，这些药物在治疗2型糖尿病和肥胖方面具有治疗潜力。现在需要进一步的试验来在临床实践中验证它们。

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

Diabetes Therapy Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

6.90

自引率

7.90%

发文量

130

审稿时长

6 weeks

期刊介绍： Diabetes Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all areas of diabetes. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Diabetes Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.