Updated October 29, 2007

Exenatide and Pramlintide
New Meds on the Block

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

Potential side effects. The most common side effect experienced with pramlintide is mild to moderate nausea. Starting pramlintide at a low dose and gradually increasing it once the nausea subsides (often after about three days) can enable a person to work up to a therapeutic dose. Nausea may also occur in people who continue to eat beyond the point of fullness. Other possible side effects include vomiting, upset stomach, decreased appetite, headache, tiredness, and dizziness. As mentioned earlier, use of pramlintide may cause some weight loss.

By itself, pramlintide does not cause low blood glucose. However, when used along with insulin, there is a risk of low blood glucose occurring, generally about three hours after the two drugs are administered. You and your diabetes care team should work together to find a dose of insulin and pramlintide that does not cause low blood glucose.

Precautions. Pramlintide should not be used by people with hypoglycemia unawareness (the inability to sense early signs of low blood glucose) or gastroparesis. It should also not be used by people who are allergic to pramlintide acetate, metacresol, D-mannitol, acetic acid, or sodium acetate.

Because pramlintide can slow the absorption of some oral medicines, it is good idea to discuss with your physician all the prescription drugs, over-the-counter drugs, and herbal or other supplements you may take. If you use any type of pain medicine, it is best to take it either one hour before or two hours after your pramlintide injection.

The safety of taking pramlintide during pregnancy is unknown. It is also not known whether pramlintide passes into breast milk. For these reasons, any women who becomes pregnant (or is considering becoming pregnant) while taking pramlintide should talk to her health-care provider about whether to continue taking the drug. Pramlintide has not been evaluated for use in children.

Helpful tips. If you miss a dose of pramlintide, do not take it during or after your meal. Wait until the next meal, then take your usual dose of pramlintide at that meal.

The manufacturer of pramlintide recommends monitoring blood glucose before meals, two hours after starting meals, and at bedtime when using pramlintide. If your health insurance plan does not cover enough testing supplies to follow this schedule, speak to your diabetes care team about an individualized monitoring schedule.

To get the most benefit out of using pramlintide, it is important to follow the instructions for taking it exactly. Your diabetes care team should direct any necessary adjustments to your pramlintide and insulin doses. Research studies have shown that adding pramlintide to insulin for the treatment of diabetes results in a lowered HbA1c level.

Recent arrivals and on the horizon
Other incretin mimetics besides exenatide continue to be studied. Another, known as liraglutide, is currently being investigated in clinical trials. It is being developed for once-daily administration. A long-acting release formulation of exenatide is also being investigated in clinical trials. The early trial results suggest that the long-acting release formulation of exenatide may be administered once weekly or once every other week.

A drug that may become available soon, pending FDA approval, is vildagliptin (Galvus). Sitagliptin (Januvia), a similar medicine, was recently released. These drugs represent a new class of drugs that also target the incretins, or gut hormones, such as GLP-1. In your body, GLP-1 is rapidly broken down by enzymes called dipeptidyl peptidase IV (DPP-IV). The new drugs act by inhibiting DPP-IV, which prolongs the level of GLP-1 in your body. This improves insulin production and suppresses glucagon secretion, effects that signal the liver to stop producing glucose and reduce blood glucose levels after meals. Sitagliptin is taken by mouth once daily; if approved, vildagliptin will be taken in the same manner.

Stacy Griffin is a diabetes educator for Drs. Borders & Associates, PSC, an American Diabetes Association-recognized education service in Lexington, Kentucky, and John Borders is a practicing internist at Drs. Borders & Associates, PSC. Dr. Griffin is also a pharmacist at Central Baptist Hospital, also in Lexington, Kentucky.

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