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The glucokinase activator AZD6370 decreases fasting and postprandial glucose in type 2 diabetes mellitus patients with effects influenced by dosing regimen and food
AstraZeneca RandD, Sweden .
Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
AstraZeneca RandD, Sweden .
AstraZeneca RandD, Sweden .
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2012 (English)In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 98, no 3, 436-444 p.Article in journal (Refereed) Published
Abstract [en]

Aims: To investigate the pharmacodynamics, pharmacokinetics and safety of the glucokinase activator AZD6370 after 1 day of administration under fed and fasted conditions in patients with type 2 diabetes mellitus (T2DM). less thanbrgreater than less thanbrgreater thanMethods: This was a two-part study. In Part A, patients received a single oral dose of AZD6370 (20, 60 or 180 mg) 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 180 mg given in one, two or four divided doses. Plasma glucose, insulin and C-peptide changes versus placebo were assessed. less thanbrgreater than less thanbrgreater thanResults: AZD6370 provided dose-dependent reductions in plasma glucose of up to 30% versus placebo in both fasted and fed patients (p andlt; 0.001 at 60 and 180 mg doses). Insulin secretion increased with dose, but absolute increases were relatively small in the fasted versus fed state (0-4 h). Dosing AZD6370 twice or four-times over 1 day 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. less thanbrgreater than less thanbrgreater thanConclusions: AZD6370 produced dose-dependent glucose reductions and increased glucose-stimulated insulin secretion in patients with T2DM.

Place, publisher, year, edition, pages
Elsevier , 2012. Vol. 98, no 3, 436-444 p.
Keyword [en]
Glucokinase activator, Pharmacokinetics, Pharmacodynamics, Glucokinase, Type 2 diabetes mellitus
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-86895DOI: 10.1016/j.diabres.2012.09.025ISI: 000312133700016OAI: oai:DiVA.org:liu-86895DiVA: diva2:583039
Note

Funding Agencies|AstraZeneca||

Available from: 2013-01-07 Created: 2013-01-07 Last updated: 2017-12-06

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Sjöberg, Folke

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Burn CenterFaculty of Health SciencesDepartment of Plastic Surgery, Hand surgery UHLDepartment of Anaesthesiology and Surgery UHL
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