Byetta & Bydureon Side Effects

Byetta and Bydureon are popular Type 2 diabetes medications. The most common side effects of these drugs are gastrointestinal problems such as nausea and diarrhea. The U.S. Food and Drug Administration has warned about serious side effects, including pancreatitis, kidney problems and the risk of thyroid tumors.

Byetta Injection Pen
Bydureon and Byetta Side Effects
  1. Black Box Warning Thyroid c-cell tumors (Bydureon)
  2. Most Reported Side Effects In Clinical Trails Nausea and vomiting
  3. Pregnancy Safety Causes birth defects and death in animals, should be used with caution in pregnant women

Byetta and Bydureon are two injectable Type 2 diabetes drugs that contain the active ingredient exenatide. Bydureon is the extended release version of Byetta. The U.S. Food and Drug Administration also approved Bydureon BCise, which comes with an easier to use injector pen.

The most common side effects of exenatide are gastrointestinal problems such as nausea, diarrhea and vomiting. The most serious Byetta and Bydureon side effects are pancreatitis and kidney problems, and Bydureon has a black box warning — the FDA’s most serious warning — for thyroid cancer risk. Injection-site reactions may also occur with Bydureon and these may require surgery.

One unique side effect of exenatide is immunogenicity, which means people can develop antibodies to the drug, and over time, it will not be as effective at controlling blood sugar. In clinical trials, researchers found antibodies in about 90 percent of patients. If sugar levels worsen while using these drugs, patients should speak with their doctor about trying a different drug, according to the prescribing information.

Common Side Effects and Reports to the FDA

The most common side effects of Bydureon and Byetta occurred in 5 percent or more of clinical trial participants. Side effects may occur more frequently when people take higher doses of the drugs or take them with other antidiabetic drugs or insulin.

Nausea, for example, occurred in 8 percent of people who took Byetta during clinical trials. Combining the drug with metformin increased that number to 44 percent, according to AstraZeneca’s Byetta website.

Common side effects include:
  • Nausea
  • Dizziness
  • Vomiting
  • Diarrhea
  • Headache
  • Dizziness
  • Injection site reactions (Bydureon)
  • Jittery feelings
  • Indigestion
  • Constipation
  • Hypoglycemia
  • Weakness or lack of energy
  • Gastroesophageal reflux disease

An October 2016 study in Diabetes Care found gastrointestinal side effects of exenatide were mild to moderate in severity and mostly went away within a few days. In some people, diarrhea, nausea and vomiting peaked by the eighth week of treatment.

Since the drugs hit the market, drugmakers have received reports of additional possible side effects. These are called postmarketing side effects, and some of them are serious.

Reports include hypersensitivity reactions (skin rashes, difficulty breathing and swelling), abdominal pain, hair loss, kidney problems and severe pancreatitis. One desirable side effect for patients in a 2009 study was a small weight loss of about 7 pounds to 13 pounds over 52 weeks, according to researchers at Oregon Health and Science University.

People report many of these postmarketing events to the FDA’s Adverse Events Reporting System (FAERS) database. From 2005 to Sept. 30, 2018, people reported 47,725 adverse events related to Byetta. The most reported adverse events in FAERS include increased blood sugar and pancreatitis.

Risk of Pancreatitis

In 2013, the FDA warned that some Type 2 diabetes drugs, including Byetta and Bydureon, may increase the risk of pancreatitis and pre-cancerous cells in the pancreas. Pancreatitis is inflammation of the pancreas and may lead to hospitalization or death.

Illustration of pancreas
The U.S. Food and Drug Administration warned in 2013 that people who take Byetta or Bydureon may have a greater chance of developing inflammation of the pancreas.

The agency based its warning on a study by Dr. Sonal Singh and colleagues published in JAMA Internal Medicine. Researchers looked at the records of 1,269 people with Type 2 diabetes who were hospitalized for acute pancreatitis. They found exenatide could double the risk of acute pancreatitis.

Labels for Bydureon and Byetta now include warnings for pancreatitis. The labels say postmarketing data links the drugs to “acute pancreatitis, including non-fatal hemorrhagic or necrotizing pancreatitis.”

The labels warn that doctors should discontinue the drugs in patients who show signs of the disease, and they should consider other therapies in patients who have had pancreatitis in the past.

From 2005 through Sept. 30, 2018, FAERS received more than 3,000 reports of pancreatitis — including necrotizing and hemorrhagic pancreatitis — in patients who took Byetta. But some studies have not found a meaningful link between the drugs and pancreatitis or pancreatic cancer.

One 2012 study published in Diabetes Technology & Therapeutics found people who used exenatide had higher rates of pancreatic cancer than those who did not take the drug. Still, the authors said it was not statistically significant.

“We found no association between exenatide use and either hospitalization for acute pancreatitis or pancreatic cancer in a large sample of privately insured U.S. patients,” the study’s authors, John A. Romley and colleagues, wrote.

Kidney Problems

In 2009, the FDA warned that Byetta and Bydureon could cause acute kidney failure and insufficiency. The agency based its warning on 78 postmarketing reports of kidney dysfunction from April 2005 to October 2008, CNN reported. Drugmakers added warnings for kidney problems to the medication labels.

Dr. Wolfgang J. Weise and colleagues documented four patients who suffered kidney failure after taking exenatide. All patients complained of nausea, vomiting and decreased fluid intake. The average time between starting to take the drug and kidney failure was between two and nine months.

Researchers said safety results for exenatide might be inaccurate because there are no long-term studies and the studies that have taken place included only a small number of patients.

“Serious adverse reactions, such as renal failure, may be more apparent when more patients are exposed to [exenatide].”

Source: Weise and colleagues, Exenatide-Associated Ischemic Renal Failure

“Although exenatide appears relatively safe, published clinical studies included only a limited number of patients for a relatively short time,” the authors wrote. “Serious adverse reactions, such as renal failure, may be more apparent when more patients are exposed to the drug.”

Of the four patients, only one was able to recover after stopping the drug. Study authors recommended that doctors monitor kidney function in people taking exenatide. The FDA also emphasized patients with kidney problems or renal disease should be careful with starting therapy or increasing the medication dose.

Bydureon and Thyroid Cancer

Bydureon has a black box warning for the risk of thyroid cancer. This warning does not extend to Byetta. From 2005 to Sept. 30, 2018, there were about 411 reports of thyroid cancers or disorders, including 18 deaths, related to Bydureon in FAERS.

Illustration of the thyroid gland.
The thyroid gland is located in the front of the neck.

In animal studies, Bydureon caused abnormal growth of thyroid C cells, according to the medication label. These can form c-cell cancers, particularly medullary thyroid carcinomas (MCT), according to an article by Dr. Michael A. Nauck and Nele Friedrich in Diabetes Care.

MCT is a rare disease and accounts for about 2 percent of thyroid cancers in women and less than 4 percent in men. It is more deadly than most thyroid cancers, and only about 40 percent of patients survive 10 years.

Fact
Researchers found people who took exenatide reported thyroid carcinomas to FAERS about five times more than those who took other diabetes drugs.
Source: Nauck and Friedrich, Do GLP-1–Based Therapies Increase Cancer Risk?

Nauck and Friedrich explained that while rats and mice may develop abnormal c-cells when exposed to exenatide, these cells do not work the same way in humans. So, they found it unlikely that exenatide would cause thyroid cancer based on animal studies.

But, there is not enough evidence to say that exenatide does not increase the risk of thyroid cancer in some people. Authors said more studies are needed and people at risk for thyroid cancer should not use drugs like Byetta or Bydureon.

Nauck and Friedrich also found FAERS showed “a significant 4.7-fold excess of thyroid carcinomas” in people who took exenatide versus patients who used other diabetes drugs. But authors questioned the accuracy of data in FAERS.

Injection-Site Reactions

Because Bydureon and Byetta are injections, they can cause injection-site reactions, though cases are rare. People who used Bydureon and Bydureon BCise extended release formulas during a study were more likely to suffer this side effect than those who used Byetta, according to a 2015 review in Diabetes Spectrum.

Bydureon uses small microspheres made out of a polymer that allow the medicine to slowly enter a patient’s blood over time, the study’s authors, S. Christopher Jones and colleagues, wrote. These may cause reactions. The FDA was aware of injection-site reactions when it originally approved Bydureon but believed they were not a serious problem and would go away quickly.

Jones and colleagues reviewed the number of injection-site nodules reported to FAERS in people who used exenatide extended-release formulas. They found 27 reports of injection-site reactions for Bydureon from January 2012 to Dec. 31 2013. These patients reported problems including bleeding, hardened nodules, inflammation, burning sensations, swelling and cellulitis.

“Serious injection-site reactions, with or without bumps (nodules), have happened in some people who use Bydureon. Some of these injection-site reactions have required surgery.”

Source: Bydureon BCise website

Of these patients, only six fully recovered from symptoms. Eight people required either surgery, hospitalization or both to treat symptoms.

According to Bydureon BCise’s maker, injection-site nodules are the most-reported problem with the medication. These may appear as bumps at the injection site. Reactions include pain, swelling, blisters, open wounds or dark scabs.

“Serious injection-site reactions, with or without bumps (nodules), have happened in some people who use Bydureon,” according to the Bydureon BCise website. “Some of these injection-site reactions have required surgery.”

Please seek the advice of a medical professional before making health care decisions.

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Michelle Llamas, Senior Content Writer
Written By Michelle Llamas Senior Writer

Michelle Llamas has been writing articles and producing podcasts about drugs, medical devices and the FDA for seven years. She specializes in fluoroquinolone antibiotics and products that affect women’s health such as Essure birth control, transvaginal mesh and talcum powder. Michelle collaborates with experts, including board-certified doctors, patients and advocates, to provide trusted health information to the public. Some of her qualifications include:

  • American Medical Writers Association (AMWA) Engage Committee and Membership Committee member
  • Centers for Disease Control and Prevention (CDC) Health Literacy certificates
  • Original works published or cited in The Lancet, British Journal of Clinical Pharmacology and the Journal for Palliative Medicine
Edited By

21 Cited Research Articles

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  4. AstraZeneca. (n.d.). What are the Side Effects of Bydureon BCise? Retrieved from https://www.bydureon.com/about-bcise/side-effects.html
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  8. Retrieved from http://care.diabetesjournals.org/content/39/10/1768
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  10. U.S. Food and Drug Administration. (n.d.). FDA Adverse Event Reporting System (FAERS) Public Dashboard. Retrieved from https://www.fda.gov/drugs/fda-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-public-dashboard
  11. Jones, S.C. et al. (2015). Injection-Site Nodules Associated With the Use of Exenatide Extended-Release Reported to the U.S. Food and Drug Administration Adverse Event Reporting System. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647172/
  12. Nauck, M.A. & Firedrich, N. (2013). Do GLP-1-Based Therapies Increase Cancer Risk? Retrieved from http://care.diabetesjournals.org/content/36/Supplement_2/S245
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  15. Weise, W.J. et al. (2009). Exenatide-Associated Ischemic Renal Failure. Retrieved from http://care.diabetesjournals.org/content/32/2/e22
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  18. Smit, J. (2013). Treatment of advanced medullary thyroid cancer. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599721/
  19. Klein, S. (2009, November 4). Diabetes drug Byetta tied to kidney problems, says FDA. Retrieved from http://www.cnn.com/2009/HEALTH/11/04/byetta.diabetes.risks/index.html
  20. U.S. Food and Drug Administration. (2013, March 14). FDA Drug Safety Communication: FDA investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes. Retrieved from https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-investigating-reports-possible-increased-risk-pancreatitis-and-pre
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