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Pharmacokinetics and Pharmacodynamics of Vildagliptin in Patients with Type 2 Diabetes Mellitus

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Abstract

Background

Vildagliptin is a dipeptidyl peptidase IV (DPP-4) inhibitor currently under development for the treatment of type 2 diabetes mellitus.

Objectives

To assess the pharmacokinetic and pharmacodynamic characteristics and tolerability of vildagliptin at doses of 10mg, 25mg and l00mg twice daily following oral administration in patients with type 2 diabetes.

Methods

Thirteen patients with type 2 diabetes were enrolled in this randomised, double-blind, double-dummy, placebo-controlled, four-period, crossover study. Patients received vildagliptin 10mg, 25mg and l00mg as well as placebo twice daily for 28 days.

Results

Vildagliptin was absorbed rapidly (median time to reach maximum concentration 1 hour) and had a mean terminal elimination half-life ranging from 1.32 to 2.43 hours. The peak concentration and total exposure increased in an approximately dose-proportional manner. Vildagliptin inhibited DPP-4 (>90%) at all doses and demonstrated a dose-dependent effect on the duration of inhibition. The areas under the plasma concentration-time curves of glucagon-like peptide-1 (GLP-1) [p < 0.001] and glucose-dependent insulinotropic peptide (GIP) [p < 0.001] were increased whereas postprandial glucagon was significantly reduced at the 25mg (p = 0.006) and l00mg (p = 0.005) doses compared with placebo. As compared with placebo treatment, mean plasma glucose concentrations were decreased by 1.4 mmol/L with the vildagliptin 25mg dosing regimen and by 2.5 mmol/L with the lOOmg dosing regimen, corresponding to a 10% and 19% reduction, respectively. Vildagliptin was generally well tolerated.

Conclusion

Vildagliptin is likely to be a useful therapy for patients with type 2 diabetes based on the inhibition of DPP-4 and the subsequent increase in incretin hormones, GLP-1 and GIP, and the decrease in glucose and glucagon levels.

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Acknowledgements

Grateful thanks to Caroline Dunstall for editorial support.

Yan-Ling He, Yibin Wang, Denise Serra, Joelle Campestrini, Gilles-Jacques Riviere and Monica Ligueros-Saylan are employees of Novartis. Carolyn F. Deacon and Jens J. Holst have served on advisory panels for Novartis, and Jens J. Holst has received research funding from Novartis. Financial support for the pharmacokinetic and pharmacodynamic analyses and manuscript preparation was provided by Novartis. The other authors have no potential conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Novartis Institute of Biomedical Research, Inc., 400 Technology Square, Building 605, 8th Floor, Room 811, Cambridge, Massachusetts, 02139-3584, USA

    Yan-Ling He PhD

  2. Novartis Pharmaceutical Corporation, East Hanover, New Jersey, USA

    Denise Serra, Yibin Wang & Monica Ligueros-Saylan

  3. Novartis Pharmaceuticals SAS, Rueil-Malmaison, France

    Joelle Campestrini & Gilles-Jacques Riviere

  4. Panum Institute, University of Copenhagen, Copenhagen, Denmark

    Carolyn F. Deacon & Jens J. Holst

  5. Diabetes and Glandular Disease Research Associates, San Antonio, Texas, USA

    Sherwyn Schwartz

  6. Cognigen Corporation, Buffalo, New York, USA

    Jace C. Nielsen

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  1. Yan-Ling He PhD
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  2. Denise Serra
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Correspondence to Yan-Ling He PhD.

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He, YL., Serra, D., Wang, Y. et al. Pharmacokinetics and Pharmacodynamics of Vildagliptin in Patients with Type 2 Diabetes Mellitus. Clin Pharmacokinet 46, 577–588 (2007). https://doi.org/10.2165/00003088-200746070-00003

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  • DOI: https://doi.org/10.2165/00003088-200746070-00003

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