The glucokinase activator AZD6370 decreases fasting and postprandial glucose in type 2 diabetes mellitus patients with effects influenced by dosing regimen and food

Abstract

AimsTo investigate the pharmacodynamics, pharmacokinetics and safety of the glucokinase activator AZD6370 after 1day of administration under fed and fasted conditions in patients with type 2 diabetes mellitus (T2DM). MethodsThis was a two-part study. In Part A, patients received a single oral dose of AZD6370 (20, 60 or 180mg) or placebo in the fasted or fed states (both n=8). In Part B, patients (n=8) received placebo and a total dose of AZD6370 180mg given in one, two or four divided doses. Plasma glucose, insulin and C-peptide changes versus placebo were assessed. ResultsAZD6370 provided dose-dependent reductions in plasma glucose of up to 30% versus placebo in both fasted and fed patients (p<0.001 at 60 and 180mg doses). Insulin secretion increased with dose, but absolute increases were relatively small in the fasted versus fed state (0–4h). Dosing AZD6370 twice or four-times over 1day gave a smoother 24-h glucose profile than single-dose. AZD6370 was rapidly absorbed. Pharmacokinetics of AZD6370 were dose-independent and unaffected by food. AZD6370 was generally well tolerated. ConclusionsAZD6370 produced dose-dependent glucose reductions and increased glucose-stimulated insulin secretion in patients with T2DM.