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A Once-Weekly Treatment for Type 2 Diabetes

Vol. 1 • Issue 1 • Page 16

Prescribing Update

Approximately 22% of U.S. residents are diagnosed with type 2 diabetes (T2DM) between ages 45 and 64.1 Patients with T2DM often have difficulty managing their blood glucose, leading to further health complications. Exenatide (Bydureon) is a glucagon-like peptide-1 (GLP-1) receptor agonist that became available in 2012. It is the first once-weekly treatment for type 2 diabetes. The drug provides a unique and multifactorial method of serum glucose reduction and offers clinical advantages beyond glucose lowering: once-weekly administration, weight reduction, improved cardiac markers and beta cell preservation.2

Treatment Principles

Eleven classes of medications for diabetes are available, and more are in development.3 Oral medications include sulfonylureas, biguandides, thiazolidinediones, dipeptidyl peptidase-IV (DDP-IV) inhibitors and alpha-glucosidase inhibitors.4 Sulfonylureas are used to acutely supplement beta cell insulin secretion, whereas biguandides prevent hepatic glucose production and increase the sensitivity of peripheral tissue to insulin. Thiazolidinediones increase insulin sensitivity, especially in adipose tissue. DDP-IV inhibitors increase GLP-1 levels that in turn increase insulin secretion. Finally, alpha-glucosidase inhibitors delay carbohydrate absorption in the gut and inhibit disaccharides, thus decreasing postprandial hyperglycemia.4

The early initiation of exogenous insulin for T2DM has become more common. Insulin increases peripheral glucose utilization and therefore decreases hepatic glucose output and lipolysis. Insulin may also be used in conjunction with various combinations of oral medications. Recently, the discovery of the incretin system has led to a novel class of antidiabetes medications, the GLP-1 receptor agonists.4,5


GLP-1 is an amino acid that enhances glucose-dependent insulin secretion as well as other antihyperglycemic functions.6 Exenatide is an injectable synthetic formulation of exendin-4, a peptide derived from the saliva of the Gila monster, a venomous lizard.

The amino acid sequence of exenatide partially overlaps that of GLP-1, thereby mimicking the effects. GLP-1 activity helps improve glycemic control whenever blood glucose is elevated and in a fasting state. It stimulates glucose-dependent insulin secretion and suppresses inappropriate glucagon secretion, which then decreases hepatic glucose production. In a fed state, GLP-1 stimulates glucose-dependent insulin secretion and suppresses postprandial glucagon secretion. This decreases hepatic glucose production, improves first-phase insulin response, slows gastric emptying, and reduces food intake.7

Exenatide is available in two preparations and brands, Byetta and Bydureon. Byetta is dosed subcutaneously twice a day and Bydureon is dosed subcutaneously once a week.5


Exenatide is contraindicated in patients with hypersensitivity to the drug or its components, type 1 diabetes, diabetic ketoacidosis, end-stage renal disease and severe gastrointestinal disease.

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Studies of exenatide during pregnancy are limited; studies in rats resulted in fetal abnormalities. Exenatide is in pregnancy category C and should only be used during pregnancy if the potential benefit outweighs the potential fetal risk. Exenatide should be used cautiously during breastfeeding.6

Adverse Reactions

Adverse reactions to exenatide include dizziness, headaches, weakness, anorexia, diarrhea, dyspepsia, nausea, pancreatitis, vomiting, reflux, hypoglycemia, excessive sweating, pruritus, urticarial rash, injection site reaction, angioedema, and anaphylaxis.2

During clinical trials, the most common adverse events associated with Bydureon were nausea, diarrhea, headache, vomiting, constipation, pruritus or nodule at the injection site, and dyspepsia. These effects occurred in less than 5% of patients.8 Drug interactions may occur with acetaminophen, digoxin, lisinopril, lovastatin and sulfonylureas.6


Bydureon offers the advantage of once-weekly dosing and studies show that it provides hemoglobin A1C reduction in the range of 1.9%.9 This is significantly better control than the shorter-acting formula for exenatide.9 Bydureon also causes less nausea and higher levels of weight loss than Byetta.3

Another benefit of this once-weekly medication is that it builds up slowly in the blood. Therefore, no titration is needed. Recent studies have shown that Bydureon may also enhance lipid levels, triglyceride levels and blood pressure, as well as beta cell preservation.9

For Prescribers

Neither formulation of exenatide should be prescribed for patients with type 1 diabetes. Concurrent use with insulin is not recommended. The safety and effectiveness of exenatide have not been established in children or adolescents.

Important considerations for Bydureon involve assessing renal and gastrointestinal function before and frequently during treatment.6 Patients with a creatinine clearance of less than 30 mL/min or in end-stage renal disease should not take this medication. Glucose levels should be monitored regularly and Hgb A1C obtained periodically. Bydureon should be discontinued if pancreatitis is suspected.

Patient Teaching

Patients should be informed that Bydureon may decrease appetite, food intake and body weight and that these changes do not warrant a dose change. Severe, persistent, unexplained abdominal pain or vomiting should be reported to a healthcare provider immediately.

Bydureon can be administered at any time during the day, with or without meals, provided that it is administered the same day every week. It can be injected in the thigh, abdomen or upper arm.

Bydureon should be stored in the refrigerator at 36 to 46 degrees Fahrenheit. Patients should be educated about infection prevention at local site injections.6

Bydureon offers a unique method of serum glucose reduction and clinical advantages that extend beyond glucose lowering. With baseline assessment, periodic monitoring and clinical interventions, this treatment can be beneficial for patients with T2DM.3


1. CDC. Percentage of Civilian, Noninstitutionalized Population with Diagnosed Diabetes, by Age, United States, 1980-2011.

2. Williams KL, Prasad-Reddy L. Incretin-based therapies: A focus on safety concerns and emerging uses. Formulary. 2012;47:369-377.

3. Rotenstein LS, et al. The Ideal diabetes therapy: What will it look like? How close are we? Clin Diabetes. 2012;30:44-53.

4. Nathan DM, et al. Medical management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy. Diabetes Care. 2009;32(1):193-203.

5. Campbell RK. Clarifying the role of incretin-based therapies in the treatment of type 2 diabetes mellitus. Clin Therapeutics. 2011;33:511-527.

6. Exenatide. In: Nursing 2012 Drug Handbook. Ambler, PA: Wolters Kluwer Health; 2012:564-565.

7. Bydureon package insert. San Diego, CA: Amylin Pharmaceuticals; 2012.

8. Exenatide extended-release (Bydureon): A once-weekly treatment (along with diet and exercise) to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings. Formulary. 2012;47:177-179.

9. Ballav C, Gough S. Bydureon: long-acting exenatide for once-weekly injection. Prescriber. 2012;23(1-2):30-33.

Katie Fetter will graduate from the family nurse practitioner program at the University of North Florida in April. She has been an RN since 2008 and became interested in Bydureon after seeing adherence problems in patients with diabetes. She has completed a disclosure statement and reports no relationships related to this article.


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