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, the FDA approved Byetta in 2005. In January 2012, the FDA approved a once-weekly exenatide injection called Bydureon — a longer-lasting version of Byetta. The FDA had previously rejected it twice in 2010 because of evidence that the drug may cause heart rhythm abnormalities.
Byetta vs. Bydureon
Bydureon is simply a longer-lasting version of Byetta taken weekly instead of twice a day.
In 2012, Bristol-Myers Squibb and AstraZeneca purchased Amylin for about $7 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. Scientists derive the synthetic hormone from the saliva of a poisonous lizard called the Gila monster found in the southwestern United States.
Byetta generated 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 expected sales of Bydureon to exceed $1 billion. The medication also costs more than many other oral diabetes medications currently on the market such as Actos (pioglitazone) or Januvia (sitagliptin). Byetta and Bydureon typically cost close to $500 a month, but actual prices may vary depending on the patient’s insurance coverage.
AstraZeneca purchased Bristol-Myers’ diabetes division in 2014 and reported sales of $327 million and $440 million for Byetta and Bydureon, respectively. When it first hit the market, the drug was proclaimed an incredible advancement in diabetes medication. But it is linked to side effects like pancreatitis, pancreatic cancer and thyroid cancer.
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.
Byetta may be prescribed alone or with metformin, a sulfonylurea (Amaryl, Glucotrol), a thiazolidinedione (Actos, Avandia), or Lantus (insulin glargine). Doctors may prescribe Byetta with DPP-4 inhibitors like Januvia, but it should not be used in people with Type 1 diabetes.
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.
Dosages and Strengths
The medication insert instructs patients to take Byetta twice a day within 60-minutes before the morning and evening meal or before the two main meals of the day. These two meals must be at least six hours apart. Health care providers should start patients on an initial dose of 5 mcg to minimize gastrointestinal side effects. After 1 month of therapy, the dose can be increased to 10 mcg.
Byetta comes in two strengths:
- 5 mcg per dose, 60 doses, 1.2 mL prefilled pen
- 10 mcg per dose, 60 doses, 2.4 mL prefilled pen
How Effective is Byetta?
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.
HbA1C, also called A1C, is measured to identify the three-month average glucose level in the blood. An A1C level of 7 or higher is considered a marker for Type 2 diabetes. People with Type 2 diabetes take medications to help lower these numbers. Results revealed that patients taking Byetta had reductions in HbA1C and reduced blood glucose, both during fasting and after eating.
In three 30-week clinical trials, people who took Byetta had an average reduction of 1 percent in A1C after three years of treatment, and the drug was effective in managing Type 2 diabetes.
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, which 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. And 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.
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.
Byetta’s Common Side Effects
In clinical trials, researchers noted the most common side effects of Byetta. These occurred in 5 percent or more of people who took the drug.
Common side effects found in clinical trials:
- Feeling jittery
- Asthenia (abnormal weakness or lack of energy)
- Dyspepsia (indigestion or chest and stomach discomfort)
Side effects found in post-marketing studies:
- Dehydration from diarrhea
- Abdominal distention
- Abdominal pain
- Alopecia (hair loss)
Byetta’s Serious Side Effects
In addition to common side effects, studies link Byetta to serious or fatal side effects. In 2009, the FDA required Amylin to add the risk of kidney damage and failure to Byetta’s warning label. The FDA found some patients who took Byetta had kidney problems that required kidney transplants or dialysis.
In addition, studies linked exenatide to cardiovascular events such as heart attack. In 2008, Amylin conducted a Canadian study for cardiovascular safety. This delayed the release of Bydureon for several years because the FDA was concerned about possible heart issues. Finally, the FDA approved Bydureon in 2012 with the condition that Amylin conduct post-market studies.
Serious side effects include:
- Acute pancreatitis (inflammation of the pancreas)
- Increased bleeding when used with warfarin
- Hemorrhagic or necrotizing pancreatitis sometimes resulting in death
- Acute or worsened chronic kidney failure
- Allergic reactions
Pancreatitis and Cancer Risks
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 damage of the pancreas, kidneys and thyroid. A 2015 review of adverse events reported to the FDA found GLP-1 agonists had higher-than-normal incidences of pancreatic and thyroid cancer.
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 revealed 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 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 post-market studies on the drug in 2009. The FDA issued an updated safety communication in 2013, saying it was still investigating the drugs’ link to pancreatitis and cancer.
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 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 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.
Pregnancy Studies in Animals
While there are no studies of Byetta use in pregnant women, researchers tested the drug in pregnant animals. According to data presented in the drug’s medication insert, Byetta caused cleft palate, skeletal abnormalities and fetal deaths. For this reason, the medication insert cautions against the use of Byetta in pregnant women. Doctors should only prescribe the drug to pregnant women if the benefit justifies the risk to the fetus.
The drug manufacturer established a Pregnancy Registry to monitor women exposed to Byetta during pregnancy. AstraZeneca encourages patients to register.