Byetta (exenatide injection) is a twice-daily injectable drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of type 2 diabetes. The drug is designed to work with diet and exercise to control blood sugar. Manufactured by San Diego-based Amylin Pharmaceuticals, Byetta was approved by the FDA in 2005. In January 2012, the FDA approved a once-weekly exenatide injection called Bydureon – a longer-lasting version of Byetta. The FDA previously rejected it twice in 2010 because of evidence that the drug may cause heart rhythm abnormalities. In 2012, Bristol-Myers Squibb purchased Amylin for about $5.3 billion.
Exenatide is part of a class of drugs called glucagonlike peptide-1 (GLP-1) receptor agonists. These drugs mimic the effects of the body’s natural GLP-1, a hormone that reacts to high blood sugar by increasing insulin production. The synthetic hormone is derived from the saliva of a poisonous lizard called the Gila monster that is found in the southwestern United States.
Byetta generates the majority of Amylin’s yearly sales and in 2011 accounted for $517.7 million (83 percent) of the company’s $621.6 million net sales. Industry analysts expect sales of Bydureon to exceed $1 billion. The drug also costs more than many other oral diabetes medications currently on the market such as Actos (pioglitazone) or Januvia (sitagliptin). Byetta costs about $170 a month, and Bydureon costs $323.44 a month.
Doctors typically prescribe Byetta or Bydureon to overweight people with type 2 diabetes, because the drug also seems to help with weight loss. People taking only Byetta lost an average of six pounds over 24 weeks, although the drug is not marketed as a weight-loss product.
In three 30-week clinical trials, people who took Byetta had an average reduction of 1 percent in A1C – the amount of glucose concentrated in a person’s blood – after three years of treatment, and the drug was effective in managing type 2 diabetes. However, the drug once proclaimed as an incredible advancement in diabetes medication is now linked to disturbing side effects like pancreatitis, pancreatic cancer and thyroid cancer. People who took Byetta and their families have since pursued litigation against Amylin and Eli Lilly, who helped market the drug.
How Does Byetta Work?
Byetta is packaged in a glass cartridge inside a pen-injector. A doctor or physician’s assistant instructs patients how to inject it. The active ingredient, exenatide, is mixed in water along with an antimicrobial agent.
Two prefilled pens come with either a 5 mcg or 10 mcg dose, and each prefilled pen delivers a 30-day supply of Byetta that should be administered twice a day. Byetta can be used alone or with metformin, a sulfonylurea (Amaryl, Glocotrol), a thiazolidinedione (Actos, Avandia), or Lantus (insulin glargine). It can also be used with DPP-4 inhibitors like Januvia. It should not be used in people with type 1 diabetes, however.
In healthy people, eating causes a rise in blood glucose and stimulates an insulin response from the pancreas. People with diabetes do not produce enough insulin to react to an increase in blood sugar. Byetta helps insulin production to regulate sugar levels.
|Byetta controls blood glucose in four ways:|
|Glucose-dependent insulin secretion. Cells in the pancreas that respond to glucose are called beta cells. In studies, Byetta increased the responsiveness of beta cells and allowed for more insulin production. Once sugar levels stabilize, the insulin production stops.|
|First-phase insulin response. The “first-phase insulin response” usually occurs within 10 minutes of raised blood glucose levels. In people with diabetes, defects in the beta cells prevent the insulin response. Byetta significantly increased the first-phase insulin response in patients taking the drug.|
|Glucagon secretion. Byetta stops excess glucagon secretion during times of hyperglycemia. Glucagon is a hormone released by the pancreas that increases blood sugar and it is the opposite of insulin.|
|Gastric emptying. By slowing gastric emptying after meals, Byetta slows the rate at which glucose enters the blood.|
Scientists conducted three 30-week, controlled clinical trials to test the effectiveness of Byetta in controlling blood glucose. In the trials, 1,446 patients whose blood sugar was poorly controlled while taking metformin alone, a sulfonylurea alone or a combination of the two were given Byetta or a placebo.
Results revealed that patients taking Byetta had reductions in HbA1C and reduced blood glucose, both during fasting and after eating. In addition, study participants in the Byetta group also lost weight.
Byetta for Weight Loss
Another way Byetta may help people with diabetes is by stimulating weight loss. Many people with type 2 diabetes are overweight or obese. This increases their risk of diabetes-related complications such as heart disease or stroke. Along with lifestyle changes, Byetta is shown to help people with diabetes lose weight and better control their blood sugar levels.
In a May 2010 study published in The American Journal of Medicine, researchers recruited 194 overweight or obese patients with type 2 diabetes. They administered Byetta to one group and a placebo to the other. People who took Byetta lost more weight than those who did not. According to Amylin’s research, the average amount of weight loss for people who took the drug with another diabetes medication was four pounds over 30 weeks. Those who took Byetta alone lost six pounds over 24 weeks.
Byetta is so effective at inducing weight loss that some people without diabetes are using it as a diet drug. Amylin and Eli Lilly say they do not encourage the “off-label” use – use not approved by the FDA – of the drug, but they funded studies of Byetta for weight loss in people with normal blood sugar. These studies showed Byetta is effective at promoting weight loss even in healthy individuals. However, the long-term use of exenatide has not been tested in people without diabetes, and doctors caution that it may be dangerous.
Serious Side Effects
There are reports of several side effects and complications related to Byetta and Bydureon, including some that require hospitalization and may be fatal. The most serious side effects are linked to damage of the pancreas, kidneys and thyroid.
Pancreatitis is a medical condition that causes the pancreas to become inflamed and swell. Severe cases can lead to hospitalization and even death – with a mortality rate of 10 to 30 percent. According to data gathered from the FDA and compiled by the Institute of Safe Medication Practices, there were more than 400 reports of acute and chronic pancreatitis in 2011 resulting from exenatide.
Data also reveal that pancreatitis is 49 times more likely to be reported in Byetta and Bydureon users than in patients who take other drugs in the same class.
In a 2011 study published in Gastroenterology, researchers found that people who took Byetta were six times more likely to report pancreatitis. The results were consistent with animal studies that also revealed an increased risk.
As a result of the increasing reports of pancreatitis in users of Byetta, the FDA required Amylin to conduct more postmarket studies on the drug in 2009, but results have yet to be reported.
|Symptoms of pancreatitis include:|
|Severe pain in the upper left side or middle of the abdomen that worsens after eating and drinking, especially if food is high in fat|
|Pain becomes more severe and lasts for several days and may radiate to the back|
|Yellowing of the skin|
This is a serious condition, and anyone who exhibits signs of pancreatitis should seek medical attention immediately. Pancreatitis can also lead to pancreatic cancer.
Pancreatic cancer is a cancer with a low survival rate because more than 80 percent of cases are diagnosed after tumors spread to other organs. Long-term survival rates are exceedingly low: about 95 percent of people succumb to the disease within five years.
Exenatide is linked to an increase in pancreatic cancer. The same 2011 study published in Gastroenterology revealed that there was an almost three-fold increase in reported cases of pancreatic cancer in users of Byetta.
The thyroid is a gland that is located in the neck, just above the collarbone. It makes hormones that are necessary for regulating the body’s metabolism, including how fast calories burn and how fast the heart beats. Depending on a number of factors, the thyroid may produce too many or too few hormones, causing weight gain or loss, rapid heartbeat and sensitivity to cold or hot temperatures. The thyroid can also develop cancer.
Clinical study results linked Byetta to thyroid cancer. One study conducted by Michael Elashoff and colleagues at the University of California, Los Angeles and published in Gastroenterology revealed that people who used Byetta were almost five times more likely to develop thyroid cancer than those who took another diabetes medication, Avandia (rosiglitazone).
A review conducted by doctors at National Taiwan University College of Medicine and published in Experimental Diabetes Research found that Byetta increased the number of cancerous cells in the thyroids of mice, and the FDA Adverse Event Reporting System database supported an increased risk of thyroid cancer associated with the drug.
Other Side Effects
In 2009, the FDA required Amylin to add the risk of kidney damage and failure to Byetta’s warning label. Exenatide was also linked to cardiovascular events such as heart attack. A 2008 study was done in Canada for risk of cardiovascular events, which Amylin attempted to withhold from the FDA. This delayed the release of Bydureon for several years, until the drug was approved in 2012 with the condition that Amylin conduct postmarket studies.
|The most common side effects reported with Byetta and Bydureon are nausea and stomach upset. Others include:|
Because of reports of hundreds of cases of pancreatitis and some fatal cases of pancreatic cancer, several individuals and families pursued litigation against Amylin and Eli Lilly for failure to warn, negligence and concealing the side effects of Byetta.
Among them is Guy Riley, surviving heir of Kathleen Riley. He filed a lawsuit on her behalf in the Superior Court of California in San Diego after she died from pancreatic cancer after taking Byetta with Januvia. His complaint alleges that Kathleen Riley suffered “severe physical, economic and emotional injuries” as a result of taking Byetta. The Rileys were unaware that Byetta carried a risk of pancreatic cancer because Amylin and Eli Lilly failed to warn the public.
If you or a loved one took Byetta or Bydureon and suffered from side effects like pancreatic cancer or pancreatitis, Drugwatch can help point you in the right direction. Our Patient Advocates are available any day of the week to answer your questions about Byetta, pancreatitis and pancreatic cancer. We can also provide information to help you decide if filing a lawsuit may be right for you.