A placebo-controlled crossover study comparing the effects of nateglinide and glibenclamide on post prandial hyperglycaemia and hyperinsulaemia in patients with Type II diabetes

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Colleges, School and Institutes


Aim: This was a randomized, double blind, three period crossover study. The objective was to compare glucose, insulin and C-peptide 24 h profiles in patients with type 2 diabetes mellitus after dosing with nateglinide (given preprandially before three test meals), glibenclamide (administered once before breakfast) or placebo (given before three test meals). Methods: Fourteen patients underwent screening followed within 3 weeks by three treatment periods of 1 day, each separated by 7 days. Dosing followed a six-sequence balanced, two 3 x 3-replicated Latin square. Results: Mean peak serum insulin levels were lower after nateglinide (115 mU/l) than after glibenclamide (145 mU/l.h; p = 0.017) but higher than after placebo (79 mU/l; p = 0.001). However, peak insulin levels were reached earlier after nateglinide [mean time to peak (t(max)) 1.7 h] compared to glibenclamide (mean t(max) 2.1 h, p = 0.06). Total insulin exposure over the day was higher after glibenclamide compared with that following nateglinide (1216 vs. 1067 mU/l.h; p = 0.009). Similar findings were seen with serum C-peptide. Despite this, mean peak plasma glucose concentrations were lower following nateglinide (11.4 mmol/l from a baseline of 8.3 mmol/l) compared with glibenclamide (13.2 mmol/l from a baseline of 8.5 mmol/l; p = 0.001) and placebo (14.0 mmol/l from a baseline of 8.0 mmol/L; p <0.001). Conclusions: Nateglinide improves early prandial measures of insulin and glucose response to a standard meal, more so than glibenclamide, in people with type 2 diabetes.


Original languageEnglish
Pages (from-to)104-113
Number of pages10
JournalDiabetes, Obesity and Metabolism
Publication statusPublished - 1 Jan 2004


  • glibenclamide, nateglinide, pharmacodynamics, pharmacokinetics, type 2 diabetes

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