Dorzagliatin monotherapy in Chinese patients with type 2 diabetes: a dose-ranging, randomised, double-blind, placebo-controlled, phase 2 study

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

“…Data generated using the current dosing regimen, combined with data generated in previous SAD and MAD trials in humans, strongly support our prediction, based on PK/PD modeling, that dorzagliatin 75 mg QD seems to be the minimum effective dose to provide 24‐hour glycaemic control and improvement in β‐cell function with an optimal safety profile. Furthermore, results from the current study support the design of including the 75 mg BID group as one of the study cohorts in the 12‐week Phase II trial conducted in Chinese T2D patients …”

Glucokinase and the potential of glucokinase activation in type 2 diabetes

“…5 The most recent study of a glucokinase activator is that of dorzagliatin, administered in increasing doses to 258 people with T2D over a 12-week period. 6 In that study, there was a significant placebo-adjusted reduction in HbA1c of 0.4% and 0.8% with 50-and 75-mg doses of dorzagliatin given twice daily, from baseline levels of 8.3% and 8.5%, respectively. Fasting glucose did not fall, but 2-hour postprandial glucose fell significantly by 2.3 to 3.3 mM with dorzagliatin treatment, as well as with 75-and 100-mg once daily doses, which did not significantly affect HbA1c.…”

“…The most recent study of a glucokinase activator is that of dorzagliatin, administered in increasing doses to 258 people with T2D over a 12‐week period . In that study, there was a significant placebo‐adjusted reduction in HbA1c of 0.4% and 0.8% with 50‐ and 75‐mg doses of dorzagliatin given twice daily, from baseline levels of 8.3% and 8.5%, respectively.…”

“…Homoeostatic model assessment of insulin resistance (HOMA‐IR) fell significantly in the 75‐mg dorzagliatin twice daily group. Hypoglycemia was infrequent but did occur, with one person each in the 75‐mg once daily and 75‐mg twice daily groups having an episode of glucose <3.0 mM …”

“…Hypoglycemia was infrequent but did occur, with one person each in the 75-mg once daily and 75-mg twice daily groups having an episode of glucose <3.0 mM. 6 Will the improvement in insulin sensitivity prove clinically relevant? Will the agent be effective beyond 12 weeks?…”