The Novel, Potent, and Selective DPP-IV Inhibitor BI 1356 Significantly Lowers HbA1c after only 4 Weeks of Treatment in Patients with Type 2 Diabetes.

BI 1356 is a novel, potent, selective, and long acting DPP-IV inhibitor in development for type 2 diabetes. The safety and tolerability of 2.5, 5 and 10 mg BI 1356 administered once daily for 28 days was investigated in a randomised, double-blind, placebo controlled, multiple dose study in 77 male and female patients with type 2 diabetes aged 40 to 69 years. The effect of BI 1356 on glycaemic control was also explored. Before treatment, patients entered a 14-day washout period of previous medication. A meal tolerance test (MTT) was performed on days -1, 1, and 29 together with measurements of glucose, GLP-1 and glucagon. The effect on HbA1c reduction was explored using an ANOVA model. Treatment with BI 1356 was well tolerated. Five patients (5/16, 31%) treated with placebo and 21 patients (21/61, 34%) treated with BI 1356 experienced at least one adverse event (AE). Most AEs were mild in intensity. Nasopharyngitis and back pain (5 patients each), and upper abdominal pain and headache (3 patients each) were the most common AEs. The incidence of nasopharyngitis and back pain was comparable between placebo and BI 1356. None of the patients experienced symptoms of hypoglycaemia. Safety laboratory parameters were stable relative to baseline. After 4 weeks of treatment with BI 1356, GLP-1 levels increased up to 4-fold and glucagon concentrations were reduced by up to 24%. Compared to baseline, glucose levels were significantly reduced after the MTT by up to 105 mg⋅h/dL depending on dose. Despite the short treatment duration, the small group sizes (n = 16-26), and a low mean baseline HbA1c of 7.0%, a significant (one-sided at p<0.025) placebo-corrected mean change in HbA1c of -0.31%, -0.37%, and -0.28% was observed for the 2.5, 5, and 10 mg dose groups, respectively. In summary, treatment of type 2 diabetic patients with BI 1356 was well tolerated and safe, and resulted in a statistically significant reduction of HbA1c after only 4 weeks of treatment. [ABSTRACT FROM AUTHOR]