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Medications

BYETTA (Exenatide) is a new class of drugs called incretin mimetics, approved by the FDA in 2005. Incretins are naturally occurring "gut" hormones secreted from the intestines in response to eating. It has been known that people with type 2 diabetes are deficient in gut hormones, one of which is called GLP-1. "Mimetic" refers to the fact that BYETTA mimics this naturally occurring hormone GLP-1. BYETTA is also called a GLP-1 analog, because it is a manmade, structurally altered chemical version of the natural hormone GLP-1.

Interestingly, BYETTA was synthesized from the saliva of the Gila monster, a large desert lizard that usually eats only a few times a year; extendin-4, a substance in the lizard's saliva, allows nutrients to be stored, and the pancreas "turned off" until the lizard eats again. Scientists were able to produce a drug that behaves in humans similar to how extendin-4 did in the Gila monster. Please read the details below.

In previous answers, I explained the role of insulin and the defects involved in type 2 diabetes; I will review the basics before I continue with information on incretin mimetics:

How the body uses glucose:

• The cells in your body need glucose to function. You get glucose both from the food you eat and also from glucose that is stored in your liver.
• Every time you eat, the level of glucose in your blood rises; this stimulates the pancreas to release more insulin. Four to five hours after a meal, your blood glucose level returns to baseline. When you haven't eaten for a while and during the night when you are sleeping, your liver releases stored glucose to supply you with energy.
• Insulin is released in response to glucose in the blood.

How insulin works-it has 3 main roles:

1. Regulates the liver from releasing too much glucose (I like to say that insulin leans up against the door of the liver and only lets a little glucose out at a time). When there is enough glucose in the blood, insulin tells the liver to shut down its production of glucose.
2. Acts as a "doorman, or key" to open the doors of the cells (called receptors) and to allow glucose to enter the cells so the glucose can then be turned into energy.
3. Acts as a "traffic cop," directing some of the glucose to be stored back into the liver and the muscles, and if you eat more than you need, the excess energy is stored as fat.

There are 3 main defects in type 2 diabetes

• Insulin resistance: In essence, the body is unable to use insulin effectively. It is as if there aren't enough doors on the cell wall, or the doors are stuck, or the lock has been changed, or else once the glucose gets into the cell it doesn't know what to do.
• Increased glucose production by the liver: Usually, as soon as you begin eating, insulin tells the liver to "shut its door" and to quit releasing glucose, since you can now get glucose from the food you're eating. With diabetes, the liver doesn't shut off, so it continues to produce unnecessary glucose (due to glucagon, a hormone from the pancreas that tells the liver to release stored glucose).
• Decreased insulin production: Eventually, as diabetes progresses, the pancreas loses its ability to produce enough insulin-either it is delayed in releasing insulin, or it can't make enough-affectionately called a "pooped out pancreas."

To elaborate further:

• People with type 2 diabetes are ALSO deficient in the hormone GLP-1. Normally, within 10 minutes of eating, GLP-1 is released to enhance insulin secretion after eating, as well as to suppress glucagon-another hormone in the pancreas that tells the liver to release glucose. This is called "glucose dependent secretion" meaning that insulin is supposed to be secreted quickly and only when needed, and glucagon is supposed to be suppressed when the liver does not need to release glucose (such as during a meal).
• People with type 2 diabetes lose their "first phase" insulin response-which is the initial release of insulin that occurs to suppress the liver from releasing glucose (since it is not needed if you are eating). This first phase insulin response is necessary to be able to control blood glucose after meals.
• In addition, because of defects in chemical signaling in people with type 2 diabetes, food passes from the stomach into the intestines in a much faster rate than in people without diabetes. This rapid passing of food into the intestines results in faster food absorption, which contributes to higher blood glucose levels after meals.

How Does BYETTA Work:

While I will provide the key points about BYETTA, please be sure to visit the BYETTA website for more details as well as to discuss this fully with your healthcare team. *

• It tells the pancreas to make the right amount of insulin after you eat, to help lower your blood glucose after meals. It does this by helping the "first-phase insulin" that is released in the first 10 minutes after eating.
• It also tells the pancreas to suppress the release of glucagon - meaning that it stops the liver from making and releasing too much glucose when your body doesn't need it, especially after meals.
• It decreases insulin secretion as the blood glucose approaches normal (to prevent you from going too low).
• It slows down the digestion of food, to allow for a more gradual absorption of glucose into the intestines, which helps lower the blood glucose after meals.
• It also often reduces your appetite and the amount of food you eat. Generally, most people lose weight on this medication.
• It begins to work as soon as the first dose; two-year studies show that the effects continue over time.

Who Can Take BYETTA:

• It is indicated for people with type 2 diabetes who are taking metformin (Glucophage®), a sulfonylurea, a thiazolidinedione, a combination of metformin and a sulfonylurea, or a combination of metformin and a thiazolidinedione, but have not achieved adequate glucose control.

Who Should Not Take BYETTA:

BYETTA should NOT be used by people who:

• Have type 1 diabetes.
• Have end stage kidney disease, severe kidney disease, or severe gastrointestinal disease.
• Are pregnant or breastfeeding.
• Are children, because BYETTA has not been studied in children.

What are the Side Effects of BYETTA:

• The most common side effects include nausea, vomiting, diarrhea, dizziness, headache, feeling jittery, and acid stomach. Nausea is most common when first starting BYETTA, but decreases over time in most people.
• Byetta may reduce your appetite, the amount of food you eat, and your weight.
• BYETTA can increase the risk of hypoglycemia, when used with a sulfonylurea. Your healthcare team should review hypoglycemia with you, and usually they will reduce your dose of sulfonylurea as well.
• There have been reports of acute pancreatitis in patients taking BYETTA, and an association between BYETTA and acute pancreatitis is suspected in some of these cases. Acute pancreatitis is a potentially serious condition that requires immediate medical attention. You should be alert to the signs and symptoms of acute pancreatitis, which include unexplained persistent severe abdominal pain, which may or may not be accompanied by vomiting. If such symptoms occur, you should seek prompt medical care. Tests are required to confirm pancreatitis. If pancreatitis is suspected, your doctor will stop your BYETTA.

How Do You Take BYETTA:

• BYETTA comes in a prefilled injection pen, with pre-measured doses of either 5 micrograms (mcg) or 10 mcg. Each pen has 60 doses to provide 30 days of twice daily injections.
• You inject BYETTA twice daily-once before your morning and evening meals (or before the two main meals of the day, at least 6 hours or more apart). After the injection, you should eat your meal anytime during the following 60 minutes.
• The usual starting dose is 5 mcg twice a day for at least 30 days. Based on your individual response, your healthcare professional may increase your dose to 10 mcg twice daily after one month of therapy.
• For those who are taking a sulfonylurea, when BYETTA is added, a reduction in the dose of sulfonylurea may be necessary to reduce the risk of hypoglycemia.
• Storage information: Until first use, BYETTA should be stored in the refrigerator, between 36 degrees F and 46 degrees F. After first use, you can keep a BYETTA pen at a temperature not to exceed 77 degrees F. Do not freeze. BYETTA should be protected from light. Throw away a used BYETTA pen after 30 days, even if some medicine remains in the pen. Do not store the pen with the needle left on, as medicine may leak from the pen, or air bubbles may form in the cartridge.
• NOTE: BYETTA slows stomach emptying and may affect medicines that need to pass through the stomach quickly, so be sure to ask your healthcare team if any of the medications you take need to be changed.

Summary:

BYETTA has been well received by the medical community despite the fact that it is an injection, due to the favorable effects of lowering post meal blood glucose, minimizing risk of hypoglycemia, and helping with weight loss. There are other incretin mimetics under development as well, including a longer acting formulation. Stay tuned for further updates.

I have provided only the most important information. After you have reviewed this information, please talk to your healthcare team to see if it is right for you. Should you decide to try BYETTA, note that this is a prescription drug, and that you should obtain instruction and guidance from a trained healthcare professional.

You can view an interactive tutorial on the BYETTA website, and you can call the Amylin Lilly Customer Support Center at: 1-800-868-1190.

*Resources for this answer are from: The BYETTA website, the BYETTA product insert, BYETTA patient information, Diabetes Self-Management Jan-Feb 2006, and Practical Diabetology, March, 2006.