Glucokinase (GK) is a glucose-sensing enzyme predominantly expressed in pancreatic beta-cells and liver that is involved in glucose homeostasis. HMS5552 is a novel allosteric GK activator (GKA) targeting both pancreatic and liver GK that has shown the ability to enhance glucose stimulated insulin release (GSIR) and suppress hepatic glucose production. In this First-in-Patient clinical study, we explore the safety, tolerability, PK, PD and glucose response profiles of HMS5552 in Chinese patients with T2DM and further characterize its mechanism of action (MOA).

HMS5552 was evaluated in a randomized, double-blind, placebo-controlled Phase 1b multiple-ascending dose study. 53 T2DM patients received HMS5552 (25, 50, 100, 150 or 200mg) or placebo twice daily orally for 8 days in hospital.