Effect of food on the pharmacokinetics of a vildagliptin/metformin (50/1000 mg) fixed-dose combination tablet in healthy volunteers

ABSTRACT

Objective: Vildagliptin is an orally active, potent and selective DPP-4 inhibitor that improves glycemic control in patients with type 2 diabetes by increasing alpha- and beta-cell responsiveness to glucose.

Research design and methods: This open-label, single-center, randomized, two-period crossover study in healthy subjects (n = 23) ages 18–45 years investigated the effect of food on the pharmacokinetics of vildagliptin and metformin following administration of a vildagliptin/metformin (50/1000 mg) fixed-dose combination tablet.

Results: Administration of the fixed-dose combination tablet following a high-fat meal had no effect on vildagliptin AUC_0–∞ (ratio of geometric mean for fed:fasted state, 1.10 [90 % CI 1.03, 1.18]), C_max (ratio of means 0.98 [90 % CI 0.85, 1.13]) or median t_max (2.5 h in fed and fasted states). The rate of absorption of metformin was decreased when given with food, as reflected by the prolonged t_max (2–4 h) and reduction in C_max (by 26 % ), but the extent of absorption was not changed. The food effect on the metformin component of the fixed-dose combination tablets was consistent with, but of a lesser magnitude compared with data stated.

Conclusions: The vildagliptin/metformin (50/1000 mg) fixed-dose combination tablet can be administered in the same manner as metformin, and can be recommended to be taken with meals to reduce the gastrointestinal symptoms associated with metformin.

Key words: :

• DPP-4 inhibitor
• Metformin
• Type 2 diabetes
• Vildagliptin

Acknowledgments

Declaration of interest: This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. All authors except for MAZ are employees of Novartis Pharmaceuticals Corporation and are eligible for Novartis stock and stock options.

All authors participated in the development, writing of the paper, and approved the final manuscript for publication. The authors take full responsibility for the content of the paper and thank Dr Richard White (Oxford PharmaGenesis Ltd) for assistance in producing the submitted version of the article.