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司美格鲁肽在非酒精性脂肪性肝炎中的应用:弥合肝脏与全身代谢功能障碍之间的差距

Survodutide in MASH: bridging the gap between hepatic and systemic metabolic dysfunction.

作者信息

Kaya Eda, Yilmaz Yusuf, Alkhouri Naim

机构信息

Department of Medicine, Knappschaftskrankenhaus Bochum, Ruhr University, Bochum, Germany.

Department of Hepatology, The Global NASH Council, Washington, DC, USA.

出版信息

Expert Opin Investig Drugs. 2024 Dec;33(12):1167-1176. doi: 10.1080/13543784.2024.2441865. Epub 2024 Dec 17.

Abstract

INTRODUCTION

Glucagon-like peptide-1 receptor (GLP-1 R) agonists have demonstrated remarkable effectiveness in the treatment of obesity and type 2 diabetes. Although these agents provide beneficial effects for metabolic dysfunction-associated steatohepatitis (MASH) through their glucose-lowering and weight-reducing properties, their efficacy in promoting fibrosis regression remains unproven. Survodutide, an investigational dual agonist that simultaneously targets both the glucagon receptor (GCGR) and GLP-1 R, has emerged as a promising therapeutic candidate for the comprehensive management of obesity and MASH. By engaging these two critical receptors, this drug has the potential to offer a broad spectrum of metabolic benefits, addressing multiple pathogenic mechanisms underlying these interrelated disorders.

AREAS COVERED

This review examines the pharmacological profile, clinical efficacy, and safety data of survodutide derived from phase 1 and 2 clinical trials.

EXPERT OPINION

Survodutide's dual agonism of the GCGR and GLP-1 R may surpass the efficacy of selective GLP-1 R agonists, demonstrating significant potential in resolving MASH and promoting fibrosis regression. The drug is generally well tolerated, with primarily manageable gastrointestinal adverse effects. As survodutide progresses through phase 3 clinical development, its potential to provide a more effective and holistic approach to treating MASH and its comorbidities may significantly improve patient outcomes and quality of life.

摘要

引言

胰高血糖素样肽-1受体(GLP-1R)激动剂在肥胖症和2型糖尿病的治疗中已显示出显著疗效。尽管这些药物通过其降糖和减重特性对代谢功能障碍相关脂肪性肝炎(MASH)产生有益作用,但其在促进纤维化消退方面的疗效仍未得到证实。司伏鲁肽是一种正在研究的双重激动剂,同时靶向胰高血糖素受体(GCGR)和GLP-1R,已成为肥胖症和MASH综合管理中一个有前景的治疗候选药物。通过作用于这两个关键受体,该药物有可能带来广泛的代谢益处,解决这些相关疾病背后的多种致病机制。

涵盖领域

本综述考察了来自1期和2期临床试验的司伏鲁肽的药理学特征、临床疗效和安全性数据。

专家观点

司伏鲁肽对GCGR和GLP-1R的双重激动作用可能超过选择性GLP-1R激动剂的疗效,在解决MASH和促进纤维化消退方面显示出巨大潜力。该药物总体耐受性良好,主要是胃肠道不良反应可控。随着司伏鲁肽进入3期临床开发阶段,其为治疗MASH及其合并症提供更有效和全面方法的潜力可能会显著改善患者的预后和生活质量。

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