Effects of Verapamil on the Pharmacokinetics and Blood Glucose-Lowering Efficacy of Saxagliptin in Normal and Streptozotocin-Nicotinamide-Induced Type 2 Diabetic Male Rats

Cardiovascular side effects are the leading cause of hospitalization/death in patients with diabetes. Saxagliptin is recommended for glycemic control in patients with Type-2-Diabetes-Mellitus (T2DM), while verapamil is preferred for cardiovascular disease. Although verapamil has been reported to exert blood glucose-lowering effects, its potential influence on the pharmacokinetics and glucose-lowering efficacy of saxagliptin has not yet been fully elucidated. This study aimed to investigate the effect of verapamil on the pharmacokinetics and blood glucose-lowering activity of saxagliptin in healthy and T2DM-model rats. Pharmacokinetic profiles of oral administration of saxagliptin (20 mg/kg) in rats with four groups (two healthy and two diabetic), with or without pretreatment of verapamil (10 mg/kg/day, PO, for 7 days), were examined. Also, blood glucose levels were analyzed to determine pharmacodynamic differences. Verapamil significantly increased the peak plasma concentration of saxagliptin in healthy and diabetic rats (from 4.8±1.07 to 6.96±1.22 μg/mL and from 6.05±1.68 to 8.24±1.2 μg/mL, respectively). Additionally, it was determined that blood glucose levels decreased with saxagliptin administration in all groups, and the decrease was higher in the verapamil-pretreated groups. The findings of this study may assist identify the best pharmacological combination effects of verapamil and saxagliptin in the treatment of diabetes.