Meglitinides - Oral Agents For Treating Diabetes Mellitus

Meglitinides

Though structurally unrelated to sulfonylureas, the meglitinide class of hypoglycemic drugs bind to the same K_ATP channel as do the sulfonylureas, but it is un-clear whether they bind to the same SUR1 subunit within the K_ATP complex. As a class, the meglitinides are incapable of stimulating insulin secretion in nutrient-starved β-cells, but in the presence of glucose, they demonstrate hypoglycemic effects by augmenting the release of insulin. Consequently, meglitinides seem rel-atively unlikely to cause fasting hypoglycemia.

Repaglinide (Prandin), a member of the meglitinide class, is approved for monotherapy or in combination with metformin. Repaglinide is taken before each meal, three times a day, and is rapidly absorbed; it is metabo-lized by the liver and has a half life of an hour. Insulin levels transiently rise postprandially after repaglinide administration but generally return to baseline by the next meal. Although repaglinide does not appear to of-fer any advantage over the sulfonylureas, it may be helpful in patients with a known allergy to sulfa drugs. Hypoglycemia is the most common side effect.

Nateglinide (Starlix), a newer drug in the meglitinide class, is a phenylalanine derivative that also works by binding to a specific site on the K⁺ –ATP–sensitive chan-nel on the surface of β-cells. Nateglinide binds with a higher affinity than does repaglinide and has a faster onset of action and a shorter duration of action. Like repaglinide, it is approved for both monotherapy and in combination with metformin. Nateglinide is taken three times a day before meals and achieves peak plasma levels within an hour. Nateglinide administra-tion results in plasma insulin levels that peak within 2 hours; they return to baseline by 4 hours. Nateglinide is metabolized by the liver and excreted by the kidney. The main side effect of nateglinide is hypoglycemia, though its effects on fasting insulin levels is not sub-stantially reduced.