Premium
Dorzagliatin (HMS5552), a novel dual‐acting glucokinase activator, improves glycaemic control and pancreatic β‐cell function in patients with type 2 diabetes: A 28‐day treatment study using biomarker‐guided patient selection
Author(s) -
Zhu XiaoXue,
Zhu DaLong,
Li XiaoYing,
Li YaLin,
Jin XiaoWei,
Hu TianXin,
Zhao Yu,
Li YongGuo,
Zhao GuiYu,
Ren Shuang,
Zhang Yi,
Ding YanHua,
Chen Li
Publication year - 2018
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13338
Subject(s) - postprandial , medicine , tolerability , type 2 diabetes , diabetes mellitus , gastroenterology , glucokinase , pharmacodynamics , pharmacokinetics , endocrinology , biomarker , urology , pharmacology , adverse effect , chemistry , biochemistry
Aims To investigate the pharmacokinetics and pharmacodynamics of a dual‐acting glucokinase activator, dorzagliatin, and its safety, tolerability and effect on pancreatic β‐cell function in Chinese patients with type 2 diabetes (T2D). Materials and methods A total of 24 T2D patients were selected, utilizing a set of predefined clinical biomarkers, and were randomized to receive dorzagliatin 75 mg twice or once daily (BID, QD respectively) for 28 days. Changes in HbA1c and glycaemic parameters from baseline to Day 28 were assessed. In addition, changes in β‐cell function from baseline to Day 32 were evaluated. Results Significant reductions in HbA1c were observed in both regimens on Day 28 (−0.79%, 75 mg BID; −1.22%, 75 mg QD). Similar trends were found in the following parameters, including reductions from baseline in fasting plasma glucose by 1.20 mmol/L and 1.51 mmol/L, in 2‐hour postprandial glucose by 2.48 mmol/L and 5.03 mmol/L, and in glucose AUC 0–24 by 18.59% and 20.98%, for the BID and QD groups, respectively. Both regimens resulted in improvement in β‐cell function as measured by steady state HOMA 2 parameter, %B, which increased by 36.31% and 40.59%, and by dynamic state parameter, ΔC 30 /ΔG 30 , which increased by 24.66% and 167.67%, for the BID and QD groups, respectively. Dorzagliatin was well tolerated in both regimens, with good pharmacokinetic profiles. Conclusions Dorzagliatin treatment for 28 days in Chinese T2D patients, selected according to predefined biomarkers, resulted in significant improvement in β‐cell function and glycaemic control. The safety and pharmacokinetic profile of dorzagliatin supports a subsequent Phase II trial design and continued clinical development.