The action of
repaglinide, a carbamoylmethyl
benzoic acid derivative, mimics the physiological insulin secretion that is deficient in
Type 2 diabetes mellitus.
Repaglinide stimulates
insulin release from beta-cells only in the presence of
glucose. Two placebo-controlled studies were performed to establish the effective dose range of
repaglinide. In one study,
repaglinide (0.25-4.0 mg preprandially) caused a dose-dependent decrease in
blood glucose and a non-dose-dependent increase in
insulin over 4 weeks (all doses p < 0.001 vs. placebo). In the second study,
repaglinide (0.25-8.0 mg preprandially) was titrated over 6 weeks to obtain the optimum response (fasting plasma
glucose < 8.9 mmol/L). The titration period was followed by a 12-week dose-maintenance period. At the end of the study,
repaglinide had decreased fasting plasma
glucose by 3.4 mmol/L (p < 0.05) and 2-h postprandial
blood glucose by 5.8 mmol/L (p < 0.001) versus placebo. Glycated haemoglobin (HbA1c) decreased significantly from 8.5% to 7.9% in the
repaglinide group and increased significantly from 8.1% to 9.2% in the placebo group (p < 0.001 between groups). In five 1-year, multicentre, randomized, double-blind, phase III trials,
repaglinide (0.5-4.0 mg preprandially) was compared with the sulphonylureas
glibenclamide,
glipizide and
gliclazide.
Repaglinide was more effective than
glipizide at maintaining glycaemic control and was equivalent to
glibenclamide and
gliclazide on the basis of change in HbA1c. Hypoglycaemic events were reported in 16% of
repaglinide-treated patients and 15-20% of sulphonylurea-treated patients. These data indicate that
repaglinide monotherapy, with diet and exercise, is effective in patients with
Type 2 diabetes.