Repaglinide improves blood glucose control in sulphonylurea-naive type 2 diabetes

Abstract

The prandial glucose regulator repaglinide has a rapid onset of action, a short half-life and is metabolised mainly by the liver. Here we report the findings of a 10-week, double-blind, parallel, placebo controlled, randomised trial with repaglinide in 25 diet-treated, sulphonylurea-naïve patients with Type 2 diabetes. Repaglinide was titrated, based on capillary blood glucose, from 0.5 mg to a maximum of 4 mg, preprandially with breakfast and dinner. After 10 weeks, repaglinide was associated with a decrease in HbA(1c) of 2.3%Hb relative to the placebo group (P=0.018). This reflected a 30% decrease within the repaglinide group from a mean HbA(1c) of 7.0 to 4.9%Hb (P<0.002). Repaglinide was also associated with a decrease in fructosamine, by 0.88 mmol/l, relative to placebo (P<0.001), with a 20% decrease (from 3.80 to 3.04 mmol/l) within the repaglinide group (P<0.001). Fasting and postprandial blood glucose concentrations decreased in association with repaglinide by 3.6 and 6.4 mmol/l, respectively, relative to placebo (P<0.001 in each case). Within the repaglinide group fasting and postprandial blood glucose decreased by 3.9 and 6.2 mmol/l, respectively (P<0.001 in each case). The number of patients reporting hypoglycaemia in the repaglinide group was similar to placebo (15 vs. 20, respectively; NS). Test meal assessments confirmed that repaglinide effectively controls glucose levels by stimulating mealtime insulin secretion. Fasting serum insulin concentration was not raised compared to baseline or placebo during repaglinide therapy, albeit that fasting glucose levels were decreased by repaglinide. Twice-daily meal-related insulin secretagogue therapy with repaglinide, a new short and rapid-acting prandial glucose regulator, is capable of improving all measures of glycaemic control without increased hypoglycaemia or fasting hyperinsulinaemia.