The preclinical results also showed that ranolazine increased glucose-stimulated insulin secretion (GSIS) in a dose-dependent manner in isolated islets. Acute administration of ranolazine to animals also significantly increased GSIS in the presence of a glucose load (p<0.05). Peak increases in insulin levels from ranolazine were similar to those seen with glibenclamide, a sulfonylurea used as a positive control. Unlike glibenclamide, in the absence of glucose ranolazine did not have any effect on insulin secretion. The company believes that the increase in glucose-stimulated insulin secretion (GSIS) seen with Ranexa (ranolazine) may contribute to the statistically significant reductions in hemoglobin A1c (HbA1c) levels observed with Ranexa in cardiovascular patients with diabetes from the Phase III Carisa (n=189 with angina and diabetes) and Merlin-Timi 36 (n=2,220 with acute coronary syndromes and diabetes) clinical trials. In Carisa, Ranexa reduced HbA1c levels by an average of up to 0.7% points. In Merlin-Timi 36, Ranexa lowered HbA1c versus placebo by an average of 0.43% points at four months in patients with a mean baseline HbA1c level of 7.5%. Luiz Belardinelli, senior vice president of pharmacological translational and biomedical research at CV Therapeutics, said: "These data provide important additional information on the potential underlying mechanism which may be responsible for significant HbA1c reductions without associated hypoglycemia in both the Carisa and Merlin-Timi 36 studies."