Authors: He, Yan-Ling¹; Serra, Denise²; Wang, Yibin²; Campestrini, Joelle³; Riviere, Gilles-Jacques³; Deacon, Carolyn F.⁴; Holst, Jens J.⁴; Schwartz, Sherwyn⁵; Nielsen, Jace C.⁶; Ligueros-Saylan, Monica²

Source: Clinical Pharmacokinetics, Volume 46, Number 7, 2007 , pp. 577-588(12)

Publisher: Adis International

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 100mg 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 100mg 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 100mg (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 100mg 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.

Keywords: CD26 antigen antagonists; CD26 antigen antagonists; Type 2 diabetes mellitus; Vildagliptin; Vildagliptin

Document Type: Research article

Affiliations: 1: 1 Novartis Institutes for BioMedical Research, Inc., Cambridge, Massachusetts, USA 2: 2 Novartis Pharmaceutical Corporation, East Hanover, New Jersey, USA 3: 3 Novartis Pharmaceuticals SAS, Rueil-Malmaison, France 4: 4 Panum Institute, University of Copenhagen, Copenhagen, Denmark 5: 5 Diabetes and Glandular Disease Research Associates, San Antonio, Texas, USA 6: 6 Cognigen Corporation, Buffalo, New York, USA

Publication date: 2007-01-01

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• By this author: He, Yan-Ling ;  Serra, Denise ;  Wang, Yibin ;  Campestrini, Joelle ;  Riviere, Gilles-Jacques ;  Deacon, Carolyn F. ;  Holst, Jens J. ;  Schwartz, Sherwyn ;  Nielsen, Jace C. ;  Ligueros-Saylan, Monica

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