Introduction

There is a new oral medication on the market for the treatment of type 2 diabetes. The new drug is called Starlix® (nateglinide) and is being marketed by Novartis Pharmaceutical Corp. Starlix was approved by the U.S. Food and Drug Administration (FDA) in December 2000. The early indications are that Starlix may provide better long-term control of blood sugar levels than other oral diabetes medications.

Following a meal, insulin is produced by the beta cells of the pancreas to take up sugar, also called glucose, from the blood into various cells, mostly liver, muscle, and fat cells. The glucose can then be used as a source of energy by the body. In type 2 diabetes, cells in the body do not respond to insulin the way they should. Cells become insensitive to insulin, which means that they do not take up as much glucose from the blood as they should. This results in high blood glucose levels, also known as hyperglycemia. Having hyperglycemia, even for just short periods of time over years, can lead to many problems involving the heart, eyes, kidneys, and more. Therefore, it is very important for people with diabetes to check their blood glucose level often to avoid going into hyperglycemia. The oral diabetes medications, such as Starlix, have been developed to assist the diabetes patient with keeping their blood glucose levels under control.

How does Starlix work?

Starlix comes from an amino acid called D-phenylalanine, and works by causing the beta cells in the pancreas to produce insulin. The sulfonylureas class of diabetes medications, including such drugs as Diabeta® and Micronase® (glyburide), Glucotrol®, and Amaryl®, also work by causing insulin production. However, there are two major difference between Starlix and the sulfonylureas. The first is that Starlix causes insulin to be produced much faster than the sulfonylureas do. This means that Starlix should be taken much closer to mealtimes than the sulfonylureas, because the body will begin producing insulin in a much shorter time period. The second difference is that the effects of Starlix do not last as long as the effects of the sulfonylureas. The effects of Starlix appear to wear off in less than one hour, compared to sulfonylureas which will continue to stimulate insulin production for several hours after being taken.

One advantage of a short duration of action is that there is less risk of hypoglycemia, or low blood glucose levels. Another advantage is that Starlix appears to be less likeley to cause the beta cells of the pancreas to "burn out."

When a person eats, the carbohydrates in the food are quickly converted by the body to glucose, resulting in a sharp increase in blood glucose levels. The "rapid on, rapid off," way in which Starlix works has been shown to help lower these sharp spikes in blood glucose which occur following a meal. The early studies that have been done seem to indicate that Starlix may provide better control of long-term blood glucose levels than some of the other diabetes medications, based upon measurements of patients' hemoglobin A1c. (See "An Overview of Hemoglobin A1c" for more information) The long-term decrease in blood glucose levels may help lower a diabetic patient's risk of developing problems with the eyes, kidneys, and heart.

Side effects and the future of Starlix

There have been no major side effects reported with the use of Starlix. While it is possible for Starlix to lead to hypoglycemia, the risk of low blood glucose levels actually occurring due to Starlix is quite low. As mentioned before, this is mostly due to the effects of Starlix lasting for less than one hour.

The FDA has approved Starlix to be used both alone and in combination with Glucophage® (metformin). It is not known exactly how Glucophage works, but some thoughts are that Glucophage works in several ways to decrease the amount of glucose in the body and to increase the effectiveness of insulin. Studies have shown there is a greater decrease in hemoglobin A1c when Starlix and Glucophage are used together.

Starlix has just begun to be available in some pharmacies throughout the United States. Novartis has also filed a submission for marketing approval with the European Medicines Evaluation Agency. There is no word as to when Starlix might be approved for marketing in Europe. Several countries, including Japan, Switzerland, Brazil, Mexico, and Venezuela, have already approved the use of Starlix.

There is not yet enough information to know just how well Starlix will help type 2 diabetes patients control their blood glucose, especially over a period of several years. The early indications are that Starlix will be very beneficial in producing long-term control of blood glucose, either by itself or in combination with Glucophage.

Brian E. Gulbis, Pharm.D.
Email: c-dunbar@onu.edu

Brian Gulbis is a recent graduate of Ohio Northern University, and is currently a pharmacy practice resident at the Medical University of South Carolina.