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October 9, 2009
Updated November 14, 2014.
Editor’s Note: This is the tenth post in our miniseries about diabetes drugs. Tune in on October 16 for the next installment.
This class of drugs, also known as the nonsulfonylurea secretagogues, is relatively new compared to the sulfonylureas (chlorpropamide [brand name Diabinese], glyburide [DiaBeta, Glynase, Micronase], glipizide [Glucotrol], glipizide extended-release [Glucotrol XL], and glimepiride [Amaryl]), with the first meglitinide being approved by the U.S. Food and Drug Administration in 1997.
Meglitinides act in a similar manner to the sulfonylureas but with a few major differences. For example, meglitinides bind to the sulfonylurea receptor in beta cells (the insulin-producing cells of the pancreas), but at a different part of the receptor than the sulfonylureas do. The interaction of the meglitinides with the receptor is not as “tight” as that of the sulfonylureas, translating to a much shorter duration of action and a higher blood glucose level needed before the drugs produce insulin secretion from the pancreas.
There are currently two meglitinides available in the United States — repaglinide (Prandin) and nateglinide (Starlix). Both are approved for use alone and in combination with other oral diabetes drugs in people with Type 2 diabetes. The major effect of meglitinides is the reduction of after-meal blood glucose levels, which results in a reduction in HbA1c (an indicator of blood glucose control over the previous 2–3 months).
Repaglinide has been shown to be roughly as effective as the sulfonylureas at reducing HbA1c levels, causing a decrease of roughly 1.5% to 2%. Nateglinide reduces HbA1c levels by approximately 0.6% to 1.2%, but it causes fewer instances of hypoglycemia (low blood glucose) than repaglinide. Since these drugs stimulate the body’s own release of insulin, they tend to lose effectiveness over time as a person’s diabetes progresses.
In a head to head study between repaglinide and nateglinide, repaglinide used alone produced a better reduction in HbA1c and fasting plasma glucose levels than nateglinide. However, reductions in HbA1c are greatest when either of these drugs is given in combination with metformin (Glucophage and others), a thiazolidinedione (Actos, Avandia) or an alpha-glucosidase inhibitor (Precose, Glyset).
Both of these drugs have relatively short half-lives (meaning they disappear from the body fairly quickly) and must be taken roughly 1–30 minutes before each meal. The recommended starting dose for nateglinide is 60 milligrams taken three times a day prior to meals, which may need to be increased to 120 milligrams three times a day after one to two weeks. The starting dose for repaglinide for people who have not previously taken glucose-lowering medicines or for those with an HbA1c level below 8.0% is 0.5 milligrams usually taken three times a day prior to meals; for all others, the recommended starting dose is 1–2 milligrams usually taken three times a day before meals.
Repaglinide interacts with certain other drugs — particularly gemfibrozil (Lopid; a cholesterol-lowering medicine) and the combination of gemfibrozil and itraconazole (the antifungal Sporanox), which raise the blood levels of repaglinide roughly 28-fold and 72-fold, respectively. Dose adjustments of repaglinide are necessary in people with severe kidney dysfunction and moderate to severe liver dysfunction. Drug interactions are less likely with nateglinide, but this medicine should be used with caution by people who have liver dysfunction. As noted above, repaglinide is more likely to cause hypoglycemia than nateglinide, and repaglinide also causes weight gain to a greater extent than nateglinide (which has been shown to have no effect on weight in some studies).
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