Dorzagliatin add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial.

Abstract

Metformin, 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 ).

• Authors: Wenying Yang, Dalong Zhu, Shenglian Gan, Xiaolin Dong, Junping Su, Wenhui Li, Hongwei Jiang, Wenjuan Zhao, Minxiu Yao, Weihong Song, Yibing Lu, Xiuzhen Zhang, Huifang Li, Guixia Wang, Wei Qiu, Guoyue Yuan, Jianhua Ma, Wei Li, Ziling Li, Xiaoyue Wang, Jiao'e Zeng, Zhou Yang, Jingdong Liu, Yongqian Liang, Song Lu, Huili Zhang, Hui Liu, Ping Liu, Kuanlu Fan, Xiaozhen Jiang, Yufeng Li, Qing Su, Tao Ning, Huiwen Tan, Zhenmei An, Zhaoshun Jiang, Lijun Liu, Zunhai Zhou, Qiu Zhang, Xuefeng Li, Zhongyan Shan, Yaoming Xue, Hong Mao, Lixin Shi, Shandong Ye, Xiaomei Zhang, Jiao Sun, Ping Li, Tao Yang, Feng Li, Jingna Lin, Zhinong Zhang, Ying Zhao, Ruonan Li, Xiaohui Guo, Qi Yao, Weiping Lu, Shen Qu, Hongmei Li, Liling Tan, Wenbo Wang, Yongli Yao, Daoxiong Chen, Yulan Li, Jialin Gao, Wen Hu, Xiaoqiang Fei, Tianfeng Wu, Song Dong, Wenlong Jin, Chenzhong Li, Dong Zhao, Bo Feng, Yu Zhao, Yi Zhang, Xiaoying Li, Li Chen
• Journal: Nature medicine (Nat Med) Vol. 28 Issue 5 Pg. 974-981 (05 2022) ISSN: 1546-170X [Electronic] United States
• PMID: 35551292 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Blood Glucose
• Glycated Hemoglobin A
• Hypoglycemic Agents
• Pyrazoles
• Metformin
• Glucokinase
• Dorzagliatin

Topics

• Blood Glucose
• Diabetes Mellitus, Type 2
• Double-Blind Method
• Drug Therapy, Combination
• Glucokinase
• Glycated Hemoglobin (analysis, therapeutic use)
• Humans
• Hypoglycemic Agents (adverse effects)
• Metformin
• Pyrazoles
• Treatment Outcome