Abstract

Objective: To assess the effects of meal timing on the pharmacokinetics and pharmacodynamics of the dipeptidyl peptidase IV (DPP-4) inhibitor vildagliptin in Japanese patients with Type 2 diabetes. Methods: In this open-label, single-center crossover study, 12 Japanese patients with Type 2 diabetes were randomized to twice-daily vildagliptin 50 mg, administered 30 min before or immediately before breakfast and dinner for 7 days. After a 7-day washout period, patients received the other regimen. Blood samples were collected for the determination of vildagliptin, DPP-4, glucagon-like peptide-1 (GLP-1) and glucose. Results: Vildagliptin absorption appeared slower when administered 30 min before rather than immediately before meals (tmax absolute range: 1.00 – 2.00 h vs. 0.33 – 1.58 h). Vildagliptin C_max and AUC_{0–8 h} were essentially the same irrespective of meal timing (geometric mean ratio: C_max 1.08 (90% CI; 0.92 – 1.26); AUC_{0–8 h} 0.97 (90% CI; 0.91 – 1.05)). Meal timing did not affect pharmacodynamics; complete DPP-4 inhibition (> 90%) was sustained for 8 h post-dose, and plasma active glucagon-like peptide-1 levels increased 2 – 3-fold from baseline. Fasting plasma glucose (FPG) and postprandial plasma glucose (PPPG) reductions from baseline did not differ significantly with meal timing (30 min before vs. immediately before: FPG, –8.9 vs. –5.8 mg/dl; adjusted AUE_{0–4 h}, –67.0 vs. –51.0 mg×h/dl). Vildagliptin was well tolerated. Conclusions: Dosing 30 min or immediately before meals did not affect vildagliptin pharmacokinetics or pharmacodynamics in Japanese patients with Type 2 diabetes.

Author Details

Authors

• Yan-Ling He¹
• Harunobu Ito²
• Masayuki Yamaguchi²
• Shinji Terao²
• Sayaka Shimada²
• Shin Irie³
• Kaneo Sekiguchi²

Departments

• ¹ Novartis Institutes for BioMedical Research Inc., Cambridge, MA, USA, and
• ² Novartis Pharma KK, Tokyo and
• ³ Kyushu Clinical Pharmacology Research Clinic, Fukuoka, Japan

Address

Yan-Ling He, PhD DMSc
Translational Sciences-Translational Medicine
Novartis Institutes for BioMedical Research Inc.
220 Massachusetts Avenue, Building 605
Cambridge, MA 02139-3584, USA
Email: [email protected]

Citation