By: Daniel Trecroci
“People who are no longer successful on oral agents can now add Byetta [exenatide] instead of insulin,” says Anne Peters, MD, director of the USC Clinical Diabetes Programs.
That is because on April 29, 2005, Byetta (exenatide) injection was granted approval as adjunctive therapy to improve blood glucose control in people with type 2. This comes on the heels of Byetta’s maker—the team of Amylin Pharmaceuticals and Eli Lilly and Company—also receiving FDA approval for its type 1 injectable drug Symlin.
Other than having the same manufacturer and being an injectable, Byetta and Symlin are in no way similar.
Indicated for Use With Other Type 2 Meds
Byetta is indicated for individuals with type 2 diabetes who have not achieved adequate control on either metformin, a sulfonylurea or the combination. There are ongoing clinical trials assessing the effect of Byetta in combination with TZDs like Avandia and Actos, studies that are slated for completion by the end of the year. Once completed, David Kendall, MD, medical director at the International Diabetes Center in Minneapolis, Minnesota, and an investigator for the Byetta clinical studies, foresees approval of this combination as well.
First Drug of Its Kind
Amylin and Lilly say that Byetta, which is now available in pharmacies, is the first in a new class of medicines known as incretin mimetics—a new class of drugs used to fight type 2.
Incretins are naturally occurring human hormones that lower blood glucose. An incretin mimetic “mimics” the actions of incretins (namely glucagon-like peptide-1, or GLP-1), which is secreted in response to food intake. GLP-1 has multiple effects on the stomach, liver, pancreas and brain that work in concert to regulate blood glucose, slow the rate at which nutrients are absorbed in the blood and reduce food intake.
Byetta represents the first compound to take advantage of the action of unique ‘gut peptides’ such as GLP-1. Kendall notes that “Byetta takes advantage of the unique mechanism of action of these incretins to improve carbohydrate metabolism.”
Specifically, Kendall adds, “Byetta is known to stimulate insulin release, suppressing glucagon secretion and limiting appetite—all features that can enhance current therapies and fill a significant treatment gap for patients with type 2 diabetes unable to achieve glucose control with their current treatment.
Lowers Post-Meal and Fasting BGs
According to Amylin and Lilly, Byetta improves blood glucose control by lowering both after-meal and fasting glucose levels. It does this by stimulating insulin secretion only when blood glucose is high and by restoring the “first-phase insulin response,” an activity that is usually lost in patients who have type 2.
Kendall says that other therapies that help increase insulin levels (e.g., sulfonylureas and insulin) raise these insulin levels in an “unregulated fashion.” With older therapies, the higher insulin levels persist even when glucose levels fall to normal or below-normal (hypoglycemic) levels.
“The glucose-dependent nature of insulin release enhanced by Byetta results in higher insulin levels only when it is needed most,” says Kendall, “with insulin levels returning to normal as glucose returns to normal.”
Peters adds that Byetta helps return beta cell function and release of insulin to a normal state.
“By doing this, the pancreas is more capable of releasing just the right amount of insulin, instead of too little,” says Peters, adding that many of the older medications don’t fix this deficiency in insulin secretion as effectively.
Both Kendall and Peters emphasized that Byetta in and of itself does not increase the risk of low blood sugar or hypoglycemia.
Weight Loss Is Another Component of Byetta Therapy
In addition, Kendall says that weight loss was observed in a majority of patients taking Byetta. According to Kendall, “Byetta appears to have effects on both appetite and hunger—presumably due to its effects in the brain.”
“People treated with incretins have less desire for food, a reduced sense of hunger and are known to limit calorie intake,” says Kendall.
Peters thinks that Byetta causes weight loss because people feel less hungry when they take it.
“This might be because their insulin secretion is now more normal without the overshoot in insulin secretion that is normal in people with type 2 diabetes,” she says. “… I think that Byetta may have a central effect on [feeling full] or else causes other hormones to be secreted that do.”
Weight loss, Kendall emphasizes, was seen even in those individuals who did not have one of the common side effects of Byetta use—namely nausea (see below for more on these side effects). “[This suggests] that the weight loss is not due to side effects alone—but rather that Byetta can help control weight effectively even as blood glucose levels improve.”
Byetta will be sold in two disposable pen devices—one able to deliver a fixed dose injection of 5 micrograms, and the other 10 micrograms. Each pen will provide a 30-day supply.
At press time, retail value was not available. However, a Byetta spokesperson says the 5-microgram pen will be available to wholesalers at a cost of $147 per pen, while the 10-microgram pen will be available to wholesalers at $172.50 per pen.
For full prescribing information or more information about Byetta, log on to www.BYETTA.com.
What Is an Incretin Mimetic?
Byetta is the first FDA-approved drug known as an incretin mimetic.
Byetta “mimics” and exhibits the glucose-lowering actions of the human incretin hormone known as glucagon-like peptide-1 (GLP-1), which is secreted in response to food intake. GLP-1 has multiple effects on the stomach, liver, pancreas and brain that work in concert to regulate blood glucose, including:
- Stimulating the body’s ability to produce insulin in response to elevated levels of blood glucose
- Inhibiting the release of a hormone called glucagon following meals
- Slowing the rate at which nutrients are absorbed into the bloodstream
- Reducing food intake
Sources: Amylin Pharmaceuticals and Eli Lilly & Co.
Safety and Tolerability
In clinical trials, the most frequently reported adverse event associated with Byetta use was mild to moderate nausea. With continued therapy in most patients who initially experienced nausea, the frequency and severity decreased over time.
In addition, patients receiving Byetta in combination with a sulfonylurea have an increased risk of hypoglycemia. No increased risk of hypoglycemia was observed when Byetta when used in combination with metformin compared to placebo.
Patients should also be advised that treatment with Byetta may result in a reduction in appetite, food intake or body weight, and that there is no need to modify the dosing regimen due to such effects.
Byetta should not be used in patients with type 1 or for the treatment of diabetic ketoacidosis. Nor is Byetta recommended for people with end-stage kidney disease or in patients with severe gastrointestinal disease.
Sources: Amylin Pharmaceuticals and Eli Lilly & Co.
Byetta’s Roots Found in Lizard Spit
According to an April 29, 2005, San Diego Union-Tribune article, John Eng, MD, was the first to discover that the venom of the Gila monster contains a hormone beneficial to people with type 2.
Eng’s studies revealed that the Gila monster, which is native to the Southwest, has venom in its saliva containing exendin-4, similar to the human gut hormone called GLP-1, which stimulates insulin secretion from the pancreas only when blood glucose is high.
Gila monsters eat only a few times a year. Immediately after eating, large quantities of exendin-4 circulate in the Gila monster’s blood. When it is not eating, it stores its nutrients in its fat tail and “turns off ” its pancreas until it is ready to secrete more exendin-4.
According to drseward.com, “ . . . an adult male Gila can consume its entire yearly energy budget in three or four meals!”
Sources: The San Diego Union-Tribune, April 29, 2005