This article reviews the clinical evidence and pharmacological rationale for repaglinide, a prandial glucose regulator. Repaglinide has a rapid onset and short duration of action - a pharmacokinetic profile that allows administration in a flexible schedule at mealtimes to limit the postprandial blood glucose excursions typical of type 2 diabetes mellitus. Placebo-controlled and comparative studies of repaglinide have demonstrated that prandial repaglinide also achieves overall glycaemic control, indicated by essential blood glucose parameters such as fasting blood glucose and hemoglobin A1c (HbA1c) levels. Regulation of postprandial glucose is of clinical importance, as this is an important independent risk factor for diabetic complications. Glycaemic control has been further improved in patients with drug-resistant type 2 diabetes when repaglinide is incorporated into combination therapy regimens with insulin-sensitizing agents such as metformin or troglitazone. There are also data to suggest that a mealtime regimen of repaglinide can reduce the likelihood of hypoglycemia compared with traditional sulphonylurea-based regimens. This benefit may be particularly marked when the patient is free to adopt a varying meal pattern. While sulphonylureas can effectively improve overall glycaemic control, their prolonged action may result in inappropriate stimulation of beta-cells during periods of relatively low blood glucose, thereby incurring the risk of hypoglycemia. Although this risk can be reduced if meals are consumed at regular intervals, such an approach places restrictions on the patient's routine and freedom to implement lifestyle measures such as caloric restriction. Repaglinide is metabolized in the liver to inactive metabolites and excreted in bile, a potential advantage for patients with renal dysfunction. In conclusion, compelling reasons for considering a prandial approach to glycaemic management include risk reductions for diabetic complications and hypoglycemia, and greater flexibility for the patient. Available data concerning repaglinide suggest that many theoretical benefits of the prandial approach to glucose regulation may be achievable in clinical practice.
Type 2 diabetes; Prandial glucose regulation; Repaglinide; Hypoglycemia
