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Exenatide and Pramlintide
New Meds on the Block

by Stacy Griffin, Pharm.D., and John Borders, M.D.

“A dream becomes a goal when action is taken toward its achievement.”

—Bo Bennett

In 2005, two new diabetes medicines—exenatide (brand name Byetta) and pramlintide (Symlin)—became available. Both medicines work differently from any previously approved diabetes drugs. Exenatide belongs to a class of drugs called incretin mimetics, so called because they imitate natural hormones called incretins. Pramlintide is a synthetic amylin analog, meaning it is chemically identical to a hormone produced by the pancreas called amylin. Both drugs lower blood glucose levels, but by somewhat different means.


The “incretin effect” was discovered many years ago, when it was noticed that the pancreas releases more insulin when a person eats carbohydrate-containing foods than it does when a comparable amount of glucose is infused intravenously, or directly into a vein. Based on this finding, it was hypothesized that factors in the gastrointestinal tract play a role in blood glucose control. Indeed, that seems to be the case.

Several hormones called incretins are released from cells in the gut in response to food. One of these is glucagon-like peptide-1, or GLP-1. Exenatide acts similarly to GLP-1 in the body. Both GLP-1 and exenatide lower blood glucose in the following ways:

  • They improve the normal release of insulin from the pancreas.
  • They suppress the secretion of glucagon, another hormone produced by the pancreas that normally stimulates the liver to release stored glucose into the bloodstream.
  • They slow the speed with which food leaves the stomach and promote a feeling of fullness.

Exenatide is approved for use in people with Type 2 diabetes who take a sulfonylurea drug, such as glyburide (DiaBeta, Micronase, Glynase), glipizide (Glucotrol, Glucotrol XL), or glimepiride (Amaryl); metformin (Glucophage, Glucophage XR, Glucovance); or a thiazolidinedione drug, such as pioglitizone (Actos) or rosiglitizone (Avandia). Exenatide rarely causes low blood glucose (hypoglycemia), and it tends to cause a gradual weight loss due to decreased calorie intake.

How to take exenatide. Exenatide comes in prefilled pens that deliver fixed, 5-microgram or 10-microgram doses. (Unlike insulin pens, exenatide pens do not require dialing in the desired dose.) Exenatide is typically taken twice daily, once before breakfast, and once before the evening meal. Each pen has 60 doses to provide 30 days of twice-daily injections. The usual starting dose is 5 micrograms (µg) twice a day. If the drug is well tolerated during the first 30 days of use, the dose may be increased to 10 µg twice a day. Exenatide must be given by injection because it is a protein. If it were taken by mouth, the drug would be digested before it could begin working.

When an exenatide pen is used for the first time, a “new pen setup” procedure must be done to prime the pen and to help remove any large bubbles that may be in it. However, the setup procedure needs to be done only once per pen; it should not be done each time a new needle is attached to the pen. Doing the new pen setup procedure more than once per pen will cause you to run out of medicine before 30 days are up.

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More articles on Oral Medicines
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