A placebo-controlled crossover study comparing the effects of nateglinide and glibenclamide on postprandial hyperglycaemia and hyperinsulinaemia in patients with type 2 diabetes

  1. A. H. Barnett1,*,
  2. D. M. Anderson2,
  3. S. Shelley3,
  4. R. Morgan4,
  5. D. R. Owens5

Article first published online: 26 JAN 2004

DOI: 10.1111/j.1462-8902.2004.00321.x

Issue

Diabetes, Obesity and Metabolism

Diabetes, Obesity and Metabolism

Volume 6, Issue 2, pages 104–113, March 2004

Additional Information

How to Cite

Barnett, A. H., Anderson, D. M., Shelley, S., Morgan, R. and Owens, D. R. (2004), A placebo-controlled crossover study comparing the effects of nateglinide and glibenclamide on postprandial hyperglycaemia and hyperinsulinaemia in patients with type 2 diabetes. Diabetes, Obesity and Metabolism, 6: 104–113. doi: 10.1111/j.1462-8902.2004.00321.x

Author Information

  1. 1

    Department of Medicine, Birmingham Heartlands Hospital, University of Birmingham, Birmingham, UK

  2. 2

    Ajinomoto Pharmaceuticals Europe Ltd, Redhill, Surrey, UK

  3. 3

    GCP Management Services Ltd, Romsey, Hampshire, UK

  4. 4

    Simbec Research Ltd, Merthyr Tydfil, UK

  5. 5

    Diabetes Research Unit, Llandough Hospital, University of Wales College of Medicine, Penarth, UK

* *Prof Anthony H. Barnett, Department of Medicine, Undergraduate Centre, Birmingham Heartlands Hospital, Birmingham, B9 5SS, UK. E-mail: anthony.barnett@heartsol.wmids.nhs.uk

Publication History

  1. Issue published online: 26 JAN 2004
  2. Article first published online: 26 JAN 2004
  3. Received 14 April 2003; returned for revision 19 August 2003; revised version accepted 10 October 2003

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Keywords:

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

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 × 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 (tmax) 1.7 h] compared to glibenclamide (mean tmax 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.

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