1861-LB：新型 GLP-1/GIP 双受体激动剂 HRS9531 在肥胖成人中的疗效和安全性--一项 2 期试验

IF 6.2 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes Pub Date : 2024-06-21 DOI:10.2337/db24-1861-lb

LIN ZHAO, DAN ZHU, DEXUE LIU, TIANRONG PAN, DONGJI WANG, YUAN HUI, HONGWEI LING, HANQIN CAI, MEIFANG ZENG, YUE ZUO, YUQI SUN, YIKE WANG, XIAOYING LI

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引用次数: 0

摘要

简介HRS9531是一种新型的GLP-1和GIP双重受体激动剂，在1期试验中显示出控制血糖和减轻体重的显著疗效。这项 2 期研究评估了 HRS9531 在无糖尿病的肥胖成人中的疗效和安全性。研究方法在这项随机、双盲、安慰剂对照的 2 期研究中，249 名体重指数为 28-40 kg/m2 的中国成年人按 1:1:1:1:1:1 的比例随机接受每周一次的 HRS9531 皮下注射（1.0 毫克、3.0 毫克、4.5 毫克和 6.0 毫克）或安慰剂，共 24 周（24W）。主要终点是第24周时体重变化的百分比。结果：第 24 周时体重与基线相比的最小二乘平均百分比变化分别为-5.4%（95% CI -7.3%至-3.5%）、-13.4%（-15.2%至-11.5%）、-14.0%（-15.9%至-12.1%）和-16.8%（-18.8%至-14.9%），而安慰剂组为-0.1%（-2.1%至1.8%）（与安慰剂的所有比较中，P<0.0001）。体重下降≥5%的参与者比例分别为52.0%、88.2%、92.0%、91.8%和10.2%。此外，HRS9531 在降低血压、改善血糖控制和降低甘油三酯水平方面的效果优于安慰剂。从基线到W24，HRS9531组收缩压的最小二乘平均变化范围为-4.46至-8.33毫米汞柱（安慰剂：-0.41毫米汞柱），HRS9531组腰围的最小二乘平均变化范围为-5.14至-12.73厘米（安慰剂：-1.82厘米）。大多数不良事件（AEs）的严重程度为轻度或中度，最常见的不良事件为恶心、腹泻、食欲下降和呕吐，主要发生在剂量递增期间。没有出现与治疗相关的严重不良反应，也没有参与者因与治疗相关的不良反应而中断治疗。结论HRS9531能有效降低体重、血压、血糖和甘油三酯，安全性良好。这些数据支持HRS9531用于肥胖症治疗的进一步临床开发。信息披露 L. Zhao：无。D. Zhu: None.D. Liu: None.T. Pan：无。D. Wang：无。Y. Hui：无。H. Ling：无。H. Cai：无。M. Zeng：江苏恒瑞医药股份有限公司员工。Y. Zuo：江苏恒瑞医药股份有限公司员工Y. Sun：江苏恒瑞医药股份有限公司员工江苏恒瑞医药股份有限公司员工Y. Wang：江苏恒瑞医药股份有限公司员工江苏恒瑞医药股份有限公司员工X. Li: None.资助江苏恒瑞医药股份有限公司。

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1861-LB: Efficacy and Safety of HRS9531, a Novel Dual GLP-1/GIP Receptor Agonist, in Obese Adults—A Phase 2 Trial

Introduction: HRS9531, a novel dual GLP-1 and GIP receptor agonist, has shown prominent efficacy in glycemic control and weight loss in phase 1 trials. This phase 2 study evaluated the efficacy and safety of HRS9531 in obese adults without diabetes. Methods: In this randomized, double-blind, placebo-controlled phase 2 study, 249 Chinese adults with a BMI of 28-40 kg/m2 were randomized 1:1:1:1:1 to receive once-weekly subcutaneous injections of HRS9531 (1.0 mg, 3.0 mg, 4.5 mg, and 6.0 mg) or placebo for 24 weeks (24W). The primary endpoint was the percentage change in body weight at W24. Results: The least-squares mean percentage change in body weight from baseline at W24 was -5.4% (95% CI -7.3% to -3.5%), -13.4% (-15.2% to -11.5%), -14.0% (-15.9% to -12.1%), and -16.8% (-18.8% to -14.9%) in the 1.0 mg, 3.0 mg, 4.5 mg, and 6.0 mg groups, respectively, compared to -0.1% (-2.1% to 1.8%) in the placebo group (P<0.0001 for all comparisons with placebo). The proportion of participants achieving ≥5% body weight reduction was 52.0%, 88.2%, 92.0%, 91.8%, and 10.2%, respectively. Additionally, HRS9531 outperformed placebo in lowering blood pressure, improving glycemic control, and reducing triglyceride levels. The least-squares mean changes from baseline to W24 in systolic blood pressure ranged from -4.46 to -8.33 mmHg in the HRS9531 groups (placebo: -0.41 mmHg) and in the waist circumference ranged from -5.14 to -12.73 cm in the HRS9531 groups (placebo: -1.82 cm). Most adverse events (AEs) were mild or moderate in severity, and the most common AEs were nausea, diarrhea, decreased appetite, and vomiting, occurring primarily during dose escalation. No serious AEs were treatment-related and no participants discontinued treatment due to treatment-related AEs. Conclusion: HRS9531 effectively reduced body weight, blood pressure, blood glucose, and triglycerides, with a favorable safety profile. These data support further clinical development of HRS9531 for obesity treatment. Disclosure L. Zhao: None. D. Zhu: None. D. Liu: None. T. Pan: None. D. Wang: None. Y. Hui: None. H. Ling: None. H. Cai: None. M. Zeng: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Y. Zuo: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Y. Sun: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. Y. Wang: Employee; Jiangsu Hengrui Pharmaceuticals Co., Ltd. X. Li: None. Funding Jiangsu Hengrui Pharmaceuticals Co., Ltd.

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来源期刊

Diabetes 医学-内分泌学与代谢

CiteScore

12.50

自引率

2.60%

发文量

1968

审稿时长

1 months

期刊介绍： Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes. However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.