ArticleDrug design, development and therapy2016
Safety, tolerability, pharmacokinetics, and pharmacodynamics of novel glucokinase activator HMS5552: results from a first-in-human single ascending dose study.
Article in Drug design, development and therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Efficacy and safety of dorzagliatin for type 2 diabetes mellitus: A meta-analysis and trial sequential analysis.Frontiers in cardiovascular medicine · 2022Pooled it
- Effects of Dorzagliatin, a Glucokinase Activator, on α- and β-Cell Function in Individuals With Impaired and Normal Glucose Tolerance.Diabetes · 2025Trial
- Trial
- Dorzagliatin in drug-naïve patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial.Nature medicine · 2022Trial
- Dorzagliatin add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial.Nature medicine · 2022 · on this mapTrial
- Resetting the glucose sensor: dorzagliatin and the evolution of glucokinase activation in diabetes therapy.BMJ open diabetes research & care · 2026Review
- A pharmacokinetic and pharmacodynamic drug-drug interaction study of dorzagliatin and empagliflozin in patients with type 2 diabetes and obesity: an open-label phase I trial.Nature communications · 2026Article
- Factors influencing the initial glycemic efficacy of dorzagliatin, a novel glucokinase activator, in type 2 diabetes.Endocrine · 2025Article
- Article
- In Vivo PK-PD and Drug-Drug Interaction Study of Dorzagliatin for the Management of PI3Kα Inhibitor-Induced Hyperglycemia.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Application of Dorzagliatin in peritoneal dialysis patients with type 2 diabetes mellitus: A case report.World journal of diabetes · 2025Article
- Dorzagliatin: A Breakthrough Glucokinase Activator Coming on Board to Treat Diabetes Mellitus.Cureus · 2024Review
- New-Generation Glucokinase Activators: Potential Game-Changers in Type 2 Diabetes Treatment.International journal of molecular sciences · 2024Review
- Population Pharmacokinetic Analysis of Dorzagliatin in Healthy Subjects and Patients with Type 2 Diabetes Mellitus.Clinical pharmacokinetics · 2023Article
- A phase I open-label clinical trial to study drug-drug interactions of Dorzagliatin and Sitagliptin in patients with type 2 diabetes and obesity.Nature communications · 2023Article
- Effects of a Novel Glucokinase Activator, Dorzagliatin, on Glycemic Control and Glucose Fluctuation in Drug-Naïve Patients with Type 2 Diabetes Mellitus.International journal of endocrinology · 2023Article
- Glucokinase as an emerging anti-diabetes target and recent progress in the development of its agonists.Journal of enzyme inhibition and medicinal chemistry · 2022Review
- Effect of renal impairment on the pharmacokinetics and safety of dorzagliatin, a novel dual-acting glucokinase activator.Clinical and translational science · 2022Article
- Article
- Pyridoxine dipharmacophore derivatives as potent glucokinase activators for the treatment of type 2 diabetes mellitus.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHMS5552, a novel fourth-generation glucokinase (GK) activator, has demonstrated promising effects on glycemic control in preclinical models of type 2 diabetes. This single ascending dose study was conducted to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of HMS5552 during its first-in-human exposure.
methodsSixty healthy subjects were enrolled. In each of six dose-cohorts (5, 10, 15, 25, 35, and 50 mg), ten subjects were randomized with eight subjects receiving the same cohort-dose of HMS5552 and two receiving placebo. Plasma HMS5552 exposure, glucose, and insulin were measured repeatedly during fasting and after a standardized meal. Assessment included safety, PK, and PD endpoints.
resultsHMS5552 showed dose-proportional increases in area under the curve 0 to the last quantifiable concentration (AUC0-t) and maximum plasma concentration (Cmax). Slopes estimated by linear regression for AUC0-t and Cmax were ~1.0 (0.932 and 0.933, respectively). Geometric mean elimination half-life ranged from 4.48 to 7.51 hours and apparent clearance ranged from 11.5 to 13.1 L/h across all doses. No significant sex effect was observed in PK parameters. HMS5552 also demonstrated dose-related PD responses in terms of maximum glucose change from baseline (%) and mean glucose area under effect curve 0-4 hours change from baseline (%) (P<0.001). Fifteen adverse events were reported by nine subjects (ten with HMS5552 and five with the placebo). All adverse events were mild in intensity and resolved without any treatment.
conclusionThis first-in-human single ascending dose study provided predicted PK of HMS5552 with dose-proportional increases in AUC0-t and Cmax, as well as dose-related glucose-lowering effects over the range of 5-50 mg in healthy subjects. HMS5552 at doses up to 50 mg in healthy subjects was safe and well-tolerated.
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