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一种名为 retatrutide 的在研药物的综述,这是一种新型三重激动剂药物,用于治疗肥胖症。

A review of an investigational drug retatrutide, a novel triple agonist agent for the treatment of obesity.

机构信息

Department of Pharmacology, Kalpana Chawla Government Medical College, Karnal, India.

出版信息

Eur J Clin Pharmacol. 2024 May;80(5):669-676. doi: 10.1007/s00228-024-03646-0. Epub 2024 Feb 17.

DOI:10.1007/s00228-024-03646-0
PMID:38367045
Abstract

BACKGROUND

Obesity is one of the critical public health problems in our society. It leads to various health conditions, such as type 2 diabetes mellitus, cardiovascular disease, hypertension, dyslipidaemia, and non-alcoholic fatty liver disease. With the rising incidence of obesity, there is a growing demand for new therapies which can effectively manage body weight and improve health.

CURRENT EVIDENCE

Currently under development, multi-receptor agonist drugs may offer a promising solution to meet this unmet medical need. Retatrutide is a novel triple receptor agonist peptide that targets the glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon-like peptide-1 receptor (GLP-1R). This novel drug has the potential to treat metabolic abnormalities associated with obesity as well as diseases resulting from it due to its distinct mechanism of action. The Phase III trial of this pipeline drug for treating type 2 diabetes mellitus, non-alcoholic fatty liver disease, and obesity started on August 28, 2023. The results of a Phase II clinical trial have demonstrated significant weight reduction in overweight and obese adults. Specifically, the trial reported an average weight loss of 17.5% and 24.4% at 24 and 48 weeks, respectively.

CONCLUSIONS

These findings hold promise for the development of effective weight loss interventions in this population group. There is a need for more phase III studies to provide sufficient clinical evidence for the effectiveness of retatrutide, as current evidence is limited to phase II studies and has yet to prove its worth in a larger population. Here, we aimed to provide an overview of retatrutide's safety and effectiveness in treating obesity.

摘要

背景

肥胖是我们社会中的一个重大公共卫生问题。它会导致多种健康问题,如 2 型糖尿病、心血管疾病、高血压、血脂异常和非酒精性脂肪肝疾病。随着肥胖发病率的上升,对于能够有效控制体重和改善健康的新疗法的需求也在不断增长。

现有证据

目前正在开发中的多受体激动剂药物可能为满足这一未满足的医疗需求提供了有希望的解决方案。Retatrutide 是一种新型三重受体激动肽,靶向胰高血糖素受体(GCGR)、葡萄糖依赖性胰岛素释放多肽受体(GIPR)和胰高血糖素样肽-1 受体(GLP-1R)。由于其独特的作用机制,这种新型药物有可能治疗与肥胖相关的代谢异常以及由此产生的疾病。该治疗 2 型糖尿病、非酒精性脂肪性肝病和肥胖的管线药物的 III 期试验于 2023 年 8 月 28 日开始。一项 II 期临床试验的结果表明,超重和肥胖成年人的体重显著减轻。具体而言,试验报告在 24 周和 48 周时分别平均减轻 17.5%和 24.4%的体重。

结论

这些发现为这一人群中有效的减肥干预措施的发展带来了希望。需要更多的 III 期研究为 retatrutide 的有效性提供充分的临床证据,因为目前的证据仅限于 II 期研究,尚未在更大的人群中证明其价值。在这里,我们旨在概述 retatrutide 在治疗肥胖症方面的安全性和有效性。

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