Dorzagliatin add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial
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Published:2022-05
Issue:5
Volume:28
Page:974-981
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ISSN:1078-8956
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Container-title:Nature Medicine
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language:en
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Short-container-title:Nat Med
Author:
Yang WenyingORCID, Zhu DalongORCID, Gan Shenglian, Dong Xiaolin, Su Junping, Li Wenhui, Jiang Hongwei, Zhao Wenjuan, Yao Minxiu, Song Weihong, Lu Yibing, Zhang Xiuzhen, Li Huifang, Wang Guixia, Qiu Wei, Yuan Guoyue, Ma Jianhua, Li Wei, Li Ziling, Wang Xiaoyue, Zeng Jiao’e, Yang Zhou, Liu Jingdong, Liang Yongqian, Lu Song, Zhang Huili, Liu Hui, Liu Ping, Fan Kuanlu, Jiang Xiaozhen, Li Yufeng, Su Qing, Ning Tao, Tan Huiwen, An Zhenmei, Jiang Zhaoshun, Liu Lijun, Zhou Zunhai, Zhang Qiu, Li Xuefeng, Shan Zhongyan, Xue Yaoming, Mao Hong, Shi Lixin, Ye Shandong, Zhang Xiaomei, Sun Jiao, Li Ping, Yang TaoORCID, Li Feng, Lin Jingna, Zhang Zhinong, Zhao Ying, Li Ruonan, Guo Xiaohui, Yao Qi, Lu Weiping, Qu Shen, Li Hongmei, Tan Liling, Wang Wenbo, Yao Yongli, Chen Daoxiong, Li Yulan, Gao Jialin, Hu Wen, Fei Xiaoqiang, Wu Tianfeng, Dong Song, Jin Wenlong, Li Chenzhong, Zhao Dong, Feng Bo, Zhao YuORCID, Zhang Yi, Li XiaoyingORCID, Chen LiORCID
Abstract
AbstractMetformin, the first-line therapy for type 2 diabetes (T2D), decreases hepatic glucose production and reduces fasting plasma glucose levels. Dorzagliatin, a dual-acting orally bioavailable glucokinase activator targeting both the pancreas and liver glucokinase, decreases postprandial glucose in patients with T2D. In this randomized, double-blind, placebo-controlled phase 3 trial, the efficacy and safety of dorzagliatin as an add-on therapy to metformin were assessed in patients with T2D who had inadequate glycemic control using metformin alone. Eligible patients with T2D (n = 767) were randomly assigned to receive dorzagliatin or placebo (1:1 ratio) as an add-on to metformin (1,500 mg per day) for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin (HbA1c) levels from baseline to week 24, and safety was assessed throughout the trial. At week 24, the least-squares mean change from baseline in HbA1c (95% confidence interval (CI)) was −1.02% (−1.11, −0.93) in the dorzagliatin group and −0.36% (−0.45, −0.26) in the placebo group (estimated treatment difference, −0.66%; 95% CI: −0.79, −0.53; P < 0.0001). The incidence of adverse events was similar between groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin and metformin combined therapy group. In patients with T2D who experienced inadequate glycemic control with metformin alone, dorzagliatin resulted in effective glycemic control with good tolerability and safety profile (NCT03141073).
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
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