Treatment with BI 1356, a Novel and Potent DPP-IV Inhibitor, Significantly Reduces Glucose Excursions after an oGTT in Patients with Type 2 Diabetes.

BI 1356 is a novel, potent, and selective DPP-IV inhibitor currently in development for type 2 diabetes. The safety, pharmacokinetics, and pharmacodynamic properties of BI 1356 were investigated in a randomised, double-blind, placebo-controlled study in patients with type 2 diabetes. Forty-seven male type 2 diabetic patients, aged 21-65 and with a BMI of 18-35 kg/m², were treated once daily with 1, 2.5, 5, or 10 mg BI 1356, or placebo for 12 days. Treatment with BI 1356 was well tolerated. The incidence of adverse events in patients treated with BI 1356 (54%) was not higher when compared to placebo (75%). There were no serious adverse events and no episodes of hypoglycaemia. BI 1356 plasma concentrations and exposure increased less than proportionally with dose. The maximum plasma concentrations of BI 1356 at steady-state ranged from 4.5 nmol/L (1 mg dose group) to 13.6 nmol/L (10 mg), with a median t[sub max] of 1.5 h. Reductions in plasma DPP-IV activity were well correlated with plasma concentrations of BI 1356. Two hours after administration of 2.5 mg BI 1356, DPP-IV activity was reduced by >80% and remained at that level at steady-state. Levels of GLP-1 were increased by more than 2-fold. Following an oGTT on day 13, 24 h after the last dose of BI 1356, area under the plasma glucose excursions were reduced by 53 (1 mg BI 1356), 106 (2.5 mg), 82 (5 mg), 111 (10 mg), and 25 (placebo) mg.h/dL, respectively. Despite the small group sizes, these reductions reached statistical significance for 2.5, 5, and 10 mg BI 1356 compared to baseline and compared to placebo (p<0.05 for both). In summary, 24 h after the last dose, DPP-IV inhibition was >70% after administration of BI 1356 doses of > 1 mg, and significant improvements in glucose parameters were observed in patients with type 2 diabetes. Given this potency and duration of action, BI 1356 has the potential to be a best in class DPP-IV inhibitor. [ABSTRACT FROM AUTHOR]