Diabetes Self-Management Blog

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 120 milligrams taken three times a day prior to meals, with a lower dose of 60 milligrams taken three times a day recommended for people who are close to their HbA1c goal. 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).

Click here for other installments of “Diabetes Drugs.”


  1. I didn’t find one of my drug listed.I take two, one being Metformin, and the unlisted one is glipizide XL, 2.5MG What can you tell me about this drug. Thanks

    Posted by Carolyn Wright |
  2. Hello Ms. Wright,

    Thanks for your comment. You can learn more about glipizide in the blog entry “Diabetes Drugs: Sulfonylureas.”

    Thank you for your interest in Diabetes Self-Management.

    Diane Fennell
    Web Editor

    Posted by Diane Fennell |
  3. I take Starlix; but I keep forgetting to take it before each meal. Usually, I easily remember to take it before breakfast. The other meals are about 50/50. Sometimes I remember it between a meal or after a meal. Any suggestions? Thanks.

    Posted by Barbara Kyle |
  4. I am 80 1/2 years old. I have type 2 diabetis.

    I take Medformin ER 500 MG 2 a day and feel very bad, I get diareahha,cramps bloating now blood in my urine. which comes and goes away.
    My Urine is Bubbly and looks soapy when it is clear.
    I have 2 srents from a blockage 10 years ago, and I have a Pace maker.

    I take plavix and blood pressure medcine.

    What other Medcine for type 2 Diabetis is good for me. I want to ge toff the Medformin ER.

    I prefer a time released medicine.

    Thank you…

    Posted by William Segale |

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