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Am Fam Physician. 2006;73(12):2213-2214


Exenatide injection (Byetta) is an incretin mimetic. Incretins are endogenous proteins that modulate the glycemic response. Exenatide enhances glucose-dependent insulin secretion by the pancreatic beta cells, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying. Its actions differ from those of insulin, sulfonylureas, biguanides, thiazolidinediones, and alpha-glucosidase inhibitors, putting exenatide in its own class of medications. Exenatide is indicated only in type 2 diabetes and is not a substitute for insulin.1

NameStarting DosageDose formApproximate monthly cost
Exenatide (Byetta)5 mcg subcutaneously twice daily within 60 minutes before meals. Dose may be increased to 10 mcg after one month.250 mcg per mL sterile solution in a 1.2-mL (60 doses of 5 mcg) or 2.4-mL (60 doses of 10 mcg) prefilled pen$191 (60 doses of 5 mcg)
$223 (60 doses of 10 mcg)


The largest clinical trial of exenatide therapy involved 733 patients who were given exenatide for 30 weeks in combination with metformin (Glucophage) and a sulfonylurea. Most adverse events were gastrointestinal; there were no reports of cardiovascular, pulmonary, hepatic, or renal adverse events. Exenatide did not increase the likelihood of hypoglycemia when added to metformin therapy.2 However, when exenatide was added to sulfonylurea therapy there was an increase in the incidence of hypoglycemic events from 3.3 percent baseline to 14.4 percent in patients receiving exenatide 5 mcg twice daily and 35.7 percent in those receiving exenatide 10 mcg twice daily.3 Exenatide has not been studied in combination with insulin, thiazolidinediones, or other hypoglycemic agents. It has not been studied with regard to its effect on patient-oriented outcomes such as diabetes-related morbidity or mortality.


In controlled trials, 7 percent of patients who took exenatide in addition to current therapy dropped out because of adverse events compared with 3 percent of patients in the placebo groups. Nausea and vomiting are the most common side effects of exenatide therapy. Diarrhea, dizziness, headache, and feeling jittery also are common. Weight gain is not associated with exenatide, and patients in clinical studies lost an average of 4.9 lb (2.2 kg) from baseline over 30 weeks.14

In one study5 comparing exenatide with insulin glargine (Lantus), almost one in 10 participants (9.7 percent) receiving exenatide dropped out because of adverse events compared with 0.7 percent of those receiving insulin glargine. Most participants who dropped out did so because of nausea (57 percent) or vomiting (17 percent).


When used in combination with a sulfonylurea, metformin, or both, exenatide produces a decrease in A1C of less than 1 percentage point. Between 24 and 46 percent of patients with an initial A1C of more than 7 percent (average 8.4 percent) will have an A1C of 7 percent or less after 30 weeks of therapy compared with 9.4 percent of patients receiving placebo (number needed to treat = 3 to 7).24 However, exenatide and insulin glargine each reduced A1C levels by an average of 1.1 percentage points, with 46 and 48 percent of patients, respectively, having an A1C of 7 percent or less after 26 weeks.5

Exenatide decreased fasting plasma glucose levels by 5 to 10 mg per dL (0.3 to 0.6 mmol per L), whereas placebo was associated with slightly increased fasting plasma glucose levels. This improvement was not associated with weight gain.24 In another study5 the reduction in fasting plasma glucose levels produced by exenatide was approximately one half that produced by insulin glargine (25.7 versus 51.5 mg per dL [1.4 versus 2.9 mmol per L], respectively).


A prefilled pen with 60 doses of exenatide (one month supply) costs approximately $191 (5-mcg doses) or $223 (10-mcg doses). One 10-mL vial of insulin glargine (100 U per mL) costs approximately $69 (not necessarily one month’s supply). Most prescription coverage plans cover exenatide with no prior approval.


Exenatide is supplied as a sterile solution for subcutaneous injection containing 250 mcg per mL. It is available as a 1.2-mL prefilled pen (60 doses, 5 mcg per dose), and as a 2.4–mL prefilled pen (60 doses, 10 mcg per dose). The subcutaneous injection should be given in the thigh, abdomen, or upper arm. The pen requires refrigeration and protection from light, and should be discarded 30 days after first use. Initial dosage is 5 mcg subcutaneously twice daily within 60 minutes before the morning and evening meals. Exenatide should not be administered after meals. The dosage may be increased to 10 mcg twice daily after one month of therapy. When exenatide is added to metformin therapy, the current dosage of metformin may be continued. When it is added to a sulfonylurea, a dosage reduction of sulfonylurea should be considered to reduce the risk of hypoglycemia; however, no standard guidelines have been established.

Bottom Line

Exenatide is an injectable treatment for type 2 diabetes. Its use requires patient education and strict monitoring of glucose levels because of the difficulty of its administration; therefore, it may not be a safe or practical option for patients who are not willing or able to administer exenatide correctly. Exenatide is an expensive, inconvenient drug that has no proven benefits over other drugs for diabetes management, including insulin.

STEPS new drug reviews cover Safety, Tolerability, Effectiveness, Price, and Simplicity. Each independent review is provided by authors who have no financial association with the drug manufacturer.

This series is coordinated by Allen F. Shaughnessy, PharmD, assistant medical editor.

A collection of STEPS published in AFP is available at

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Copyright © 2006 by the American Academy of Family Physicians.

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