Bydureon Side Effects: Weekly injection for type 2 diabetes drug Bydureon gets FDA nod, but with many constraints. The most common side effects are mild to moderate. Nausea, occurring at the start of the treatment and decreasing over time. Vomiting, diarrhea, constipation. Headache, low blood sugar levels. Itching at the site of the injection.
Meanwhile, four main studies lasting six months or more and involving 1,525 type 2 diabetes patients showed that the once-a-week diabetes injection effectively lowered sugar levels in the bloodstream.
Cited by the European Union’s Committee for Medicinal Products for Human Use (CHMP), those findings prompted the European Medicines Agency, EU’s health regulator, to approve early last year, in April 2011, Bydureon, the new diabetes injection.
And, only last month and after two previous rejections in 2010, the United States Food and Drug Administration finally approved the use of the more convenient diabetes injection—with a caveat that it was to be used as “an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.” It’s not been approved by Health Canada.
Bydureon, made by Amylin Pharmaceuticals Inc, is injected once a week, unlike similar drugs, even the company’s seven-year old diabetes medicine, Byetta, which have to be injected twice a day.
Despite the convenience the new injection offers, the U.S. health regulator has always been less enthusiastic over it, concerned over possible serious side effects.
When the FDA turned down the drug, twice in 2010, its most serious concern was that Bydureon may contribute to heart rhythm abnormalities and it asked the drug maker to study this.
Amylin complied, and a new study done in San Diego suggested this was not the case, says New York Times Health Writer Andrew Pollack in his report on the diabetes drug’s FDA approval. It wasn’t clear, however, which medical institute carried out the research.
And although it’s approved the drug, the FDA is also requiring Amylin to conduct yet another clinical trial to assess whether Bydureon increases the risk of heart attacks and other cardiovascular problems. The company has again agreed, and a trial is underway.
The same trial will also look at whether the drug increases the risk for thyroid cancer, pancreatitis and other health problems.
Serious side effects
In fact, the FDA carries a 2,000-word advisory on its website warning patients about the possible serious side effects of Bydureon: thyroid tumors and a type of thyroid cancer called medullary thyroid cancer, pancreatic or inflammation of the pancreas, hypoglycemia or low blood sugar, kidney failure and severe allergic reactions.
On a page on the “important limitations of use” of Bydureon on its site, the FDA even warns, “Because of the uncertain relevance of the rat thyroid C-cell tumor findings to humans,” Bydureon “should only be prescribed to patients for whom the potential benefits are considered to outweigh the potential risk.”
The FDA also says the new diabetes injection is “not recommended as first-line therapy for patients with diabetes.” And when it is prescribed, the agency stresses, it “should be used along with a proper diet and exercise.”
The injection isn’t also recommended for use in children, as “it’s not known if Bydureon is safe and effective in children.”
“Other antidiabetic therapies should be considered in patients with a history of pancreatitis,” the FDA also says, noting, “It’s unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using Bydureon.”
It’s also not for use in people with type 1 diabetes or people with a diabetic ketoacidosis, caused by very high blood sugar, the FDA says.
Currently, the use of Bydureon with insulin hasn’t been studied, the FDA further warns, noting that the injection is not a substitute for insulin. “The concurrent use of Bydureon with insulin has not been studied and cannot be recommended,” the FDA warns.
Weighing the benefits
Global health authorities are now grappling with a diabetes epidemic, characterized by cases of Type 2 diabetes rising nine-fold over the past 25 years.
Today, more than 300 million people worldwide suffer from diabetes, including nearly 26 million Americans, or roughly eight percent of the U.S. population. Most cases—90 to 95 percent—are of type 2 diabetes, the type linked to poor diet and exercise.
People with type 2 diabetes are unable to break down carbohydrates properly, either because their bodies don’t produce enough insulin or because they’ve become resistant to the hormone, which controls blood sugar levels.
These people—who run a higher risk for heart attacks, kidney problems, blindness and loss of limbs—often need to take many drugs with different mechanisms of action to control their blood sugar levels. Keeping track of these drugs can be a nightmare.
This is where Bydureon comes in: for many patients, a once-weekly self-injection is a welcome alternative to multiple insulin injections or even to multiple pills every day, says David Kliff, publisher of Diabetic Investor, an electronic newsletter following the diabetes industry.
“One of the biggest obstacles to better patient outcomes,” is the failure of people to consistently take their medicines, says Kliff, who has Type 1 diabetes.
“Think for a moment how much easier their lives would be by taking a drug just once a week, a drug that offers solid glucose control, does not require glucose monitoring and comes with added benefit of weight loss.”
According to Europe’s health regulators, apart from “the main benefit of Bydureon, its ability to improve glucose metabolism when added to an existing oral antidiabetic therapy…an additional benefit is the associated loss in body weight, which is in contrast to many other therapeutic options available in this setting.”
Weight loss is an important part of managing and treating diabetes; people who are obese have a higher chance of getting diabetes.
How it works
Exenatide, the active ingredient in both Bydureon and Byetta, is a hormone derived from the saliva of the Gila monster, a poisonous lizard found in Mexico and the southwestern U.S. states.
Exenatide is an ‘incretin mimetic’ that mimics the way incretins or hormones produced in the gut work—increasing the amount of insulin released by the pancreas in response to food and as a result, helping control blood glucose levels.
In both the U.S. and countries of Europe, Bydureon is indicated for the treatment of type 2 diabetes in adults, in combination with these oral therapies and when these therapies are not enough to control blood sugar:
• Metformin
• Sulphonylurea
• Thiazolidinedione
• Metformin and sulphonylurea
• Metformin and thiazolidinedione
What you should know
The new diabetes injection can cause serious side effects, including:
Low blood sugar or hypoglycemia. Your risk for getting low blood sugar is higher if you take Bydureon with other drugs to lower blood sugar, like sulfonylurea. The dose of your sulfonylurea medicine may need to be lowered while you use Bydureon. Signs of low blood sugar may include: shakiness, confusion, sweating, irritability, headache, hunger, drowsiness, fast heartbeat, weakness, feeling jittery dizziness.
Make sure that your family and other people around you a lot know how to recognize and treat low blood sugar.
Kidney failure. Bydureon may cause nausea, vomiting or diarrhea. This can lead to dehydration, which in turn can cause kidney failure—leading to the need for dialysis. This can happen even in people who have never had kidney problems before. To prevent this from happening, drink plenty of fluids and call your healthcare provider right away if you have nausea, vomiting, or diarrhea that will not go away, or if you cannot drink liquids by mouth.
Severe allergic reactions. If these happens, get medical help right away. Signs of a severe allergic reaction are:
• swelling of your face, lips, tongue, or throat
• fainting or feeling dizzy
• very rapid heartbeat
• problems breathing or swallowing
• severe rash or itching
Don’t take Bydureon if you have:
• A family member with thyroid cancer, especially medullary thyroid cancer, or multiple endocrine neoplasia syndrome type. People with these conditions already have a higher chance of developing medullary thyroid cancer.
• Pancreatitis, stones in your gallbladder (gallstones), a history of alcoholism or high blood triglyceride levels. These conditions can make you more likely to get pancreatitis—an inflammation of the pancreas that may be severe and lead to death.
• Severe problems with your stomach such as slow emptying of your stomach (gastroparesis) or problems digesting food.
• Kidney problems or have had a kidney transplant.
• Are pregnant or are planning to become pregnant. It is not known if Bydureon may harm your unborn baby. Tell your healthcare provider if you become pregnant while taking Bydureon. Amylin Pharmaceuticals, Inc. has a registry for women who take Bydureon during pregnancy. The registry’s purpose is to collect information about your health and that of your baby. If you take Bydureon at any time during pregnancy, you may enroll in this registry by calling 1-800-6339081.
• Are breastfeeding or plan to breastfeed. It is not known if Bydureon passes into your breast milk. You and your healthcare provider should decide if you will take Bydureon or breastfeed.
Stop taking Bydureon and call your healthcare provider right away if, while taking it:
• You get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath. These may be symptoms of thyroid cancer.
• You have severe pain in your stomach area that will not go away. The pain may happen with or without vomiting, and may be felt going from your abdomen through to your back. This may be a symptom of pancreatitis.
How is Bydureon used?
Bydureon is a 2 mg suspension formulation injected in the abdomen, thigh or back of the upper arm, once a week, on the same day each week.
Patients inject themselves using a kit supplied with the medicine. They should be given appropriate training and should follow the user instructions.
Price
A four doses in a monthly series of Bydureon injections is expected to cost US$323, compared with US$291 for the older Byetta—or about US$4,200 a year.
That is between the roughly US$3,400 for the low dose of Victoza, the rival drug manufactured by drug maker Novo Nordisk and US$5,000 for the high dose, said Mark Schoenebaum, an analyst at the ISI Group.
Despite the less frequent injections, Bydureon will not automatically be preferred over Victoza, the New York Times predicts.
This is partly because it is more cumbersome for a patient to prepare Bydureon for each injection, the needle used is larger than for Victoza, and on average Bydureon reduced blood sugar levels in diabetics less than Victoza, which uses a different mechanism of action, according to Amylin’s own clinical trials.
Bydureon was co-developed with Indianapolis-based Eli Lilly and Co., which also helped co-market Byetta. But news of costly delays in FDA approval sent company shares tumbling more than 50 percent, contributing to the eventual breakup of Amylin’s long-standing partnership with Eli Lilly.
The companies ended their collaboration in November, with Amylin paying US$250 million and agreeing to take over full responsibility for both Byetta and Bydureon.
Amylin shares rose after it got the thumbs up from the FDA, but the company, founded in 1987, has never been profitable from drug sales and it still faces hurdles.
Robyn Karnauskas, an analyst at Deutsche Bank, said Amylin might be a takeover candidate for a big company.