一种新的葡萄糖激酶激活剂--多扎格拉汀的最新药物开发,有望治疗 2 型糖尿病:回顾研究。

IF 3 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Journal of Diabetes Pub Date : 2024-05-23 DOI:10.1111/1753-0407.13563
Yu Jiang, Luyao Wang, Zhenhua Dong, Baotian Xia, Shuguang Pang
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引用次数: 0

摘要

2 型糖尿病(T2DM)是一种与新陈代谢有关的复杂疾病,由胰岛素抵抗和持续高血糖引起。传统的抗糖尿病药物无法满足不同糖尿病患者对血糖达标的需求,因此,急需寻找新的抗糖尿病药物来治疗 T2DM,以提高 T2DM 患者的血糖控制和预后。最近,葡萄糖激酶(GK)备受关注,被认为是一种有效的抗糖尿病药物。以多扎格拉汀为代表的葡萄糖激酶激活剂(GKA)可以激活葡萄糖激酶,并模拟其对血糖变化触发反调节反应的功能。在一项随机、双盲、安慰剂对照的 3 期试验(SEED 研究)中,Dorzagliatin 在糖尿病患者的血糖控制方面显示出巨大的潜力,并且具有良好的安全性和耐受性(DAWN 研究)。在 SEED 研究中,多扎格雷丁能显著降低糖化血红蛋白(HbA1c)1.07% 和餐后血糖 2.83 mol/L,显示出该药物在控制糖尿病患者血糖方面的巨大潜力,而且安全性和耐受性良好。SEED 研究的延伸项目 DREAM 研究证实,多扎格雷汀单药治疗可显著改善 24 小时血糖变异性,并在 46 周内将血糖在范围内的时间(TIR)提高到 83.7%。最后,多扎格拉汀联合二甲双胍的临床研究(DAWN 研究)证实,多扎格拉汀可将 HbA1c 明显降低 1.02%,餐后血糖降低 5.45 mol/L。本综述总结了 GK 和 GKA 的发展,以及这些疗法的前景、趋势、应用和不足之处,尤其是多扎格列汀临床研究的未来方向。
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Recent drug development of dorzagliatin, a new glucokinase activator, with the potential to treat Type 2 diabetes: A review study

Type 2 diabetes mellitus (T2DM) is a complicated disease related to metabolism that results from resistance to insulin and sustained hyperglycemia. Traditional antidiabetic drugs cannot meet the demand of different diabetes patients for reaching the glycemic targets; thus, the identification of new antidiabetic drugs is urgently needed for the treatment of T2DM to enhance glycemic control and the prognosis of patients suffering from T2DM. Recently, glucokinase (GK) has attracted much attention and is considered to be an effective antidiabetic agent. Glucokinase activators (GKA) represented by dorzagliatin could activate GK and mimic its function that triggers a counter-regulatory response to blood glucose changes. Dorzagliatin has shown great potential for glycemic control in diabetic patients in a randomized, double-blind, placebo-controlled Phase 3 trial (SEED study) and had a favorable safety profile and was well tolerated (DAWN study). In the SEED study, dorzagliatin significantly reduced glycosylated hemoglobin (HbA1c) by 1.07% and postprandial blood glucose by 2.83 mol/L, showing the great potential of this drug to control blood glucose in diabetic patients, with good safety and good tolerance. An extension of the SEED study, the DREAM study, confirmed that dorzagliatin monotherapy significantly improved 24-h glucose variability and increased time in range (TIR) to 83.7% over 46 weeks. Finally, the clinical study of dorzagliatin combined with metformin (DAWN study) confirmed that dorzagliatin could significantly reduce HbA1c by 1.02% and postprandial blood glucose by 5.45 mol/L. The current review summarizes the development of GK and GKA, as well as the prospects, trends, applications, and shortcomings of these treatments, especially future directions of clinical studies of dorzagliatin.

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来源期刊
Journal of Diabetes
Journal of Diabetes ENDOCRINOLOGY & METABOLISM-
CiteScore
6.50
自引率
2.20%
发文量
94
审稿时长
>12 weeks
期刊介绍: Journal of Diabetes (JDB) devotes itself to diabetes research, therapeutics, and education. It aims to involve researchers and practitioners in a dialogue between East and West via all aspects of epidemiology, etiology, pathogenesis, management, complications and prevention of diabetes, including the molecular, biochemical, and physiological aspects of diabetes. The Editorial team is international with a unique mix of Asian and Western participation. The Editors welcome submissions in form of original research articles, images, novel case reports and correspondence, and will solicit reviews, point-counterpoint, commentaries, editorials, news highlights, and educational content.
期刊最新文献
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