Pharmacology and clinical experience with repaglinide

Repaglinide (NovoNorm(R)) is a novel oral antidiabetic agent, the first of a new class of insulin secretagogues known as the prandial glucose regulato rs to be approved for use in patients with Type 2 diabetes. Prandial glucos e regulation is aimed at restoring the first-phase insulin response that fo llows consumption of a meal, which is missing in patients with Type 2 diabe tes. After repaglinide administration, the resulting insulin profile reflec ts that of healthy individuals more closely, providing tighter glycaemic co ntrol and reducing the risk of hypoglycaemic events. Repaglinide is quickly absorbed and rapidly eliminated through biliary excretion, making it suita ble for use in patients with renal impairment. It appears in the bloodstrea m within 15 to 30 min of dosing, stimulating short-term insulin release fro m the pancreatic beta-cells by binding to a unique site on the beta-cell me mbrane. Rapid elimination ensures that postprandial insulin levels quickly return to preprandial levels as the high prandial glucose level subsides. R epaglinide is given on a 'one meal, one tablet; no meal, no tablet' basis. It is particularly effective in patients who have not previously been treat ed with an oral antidiabetic agent, significantly reducing glycosylated hae moglobin (HbA(1c)) levels by 1.6%. It also offers increased mealtime flexib ility and safety, compared with other oral antidiabetic agents. As a result of the short plasma half-life and lack of accumulation of repaglinide with repeated dosing, the risk of between-meal and nocturnal hypoglycaemia is s ubstantially reduced compared with other oral antidiabetic agents. Repaglin ide acts synergistically with metformin, consistently improving glycaemic c ontrol in patients who were insufficiently controlled by metformin alone. R esults from recent studies have shown similar synergistic effects with neut ral protamine Hagedorn (NPH)-insulin or troglitazone.