Skip to Content


Pronunciation: ex-EN-a-tide
Class: Antidiabetic agent

Trade Names

- Injection, powder for suspension, ER 2 mg

- Injection, solution 250 mcg/mL


Glucagon-like peptide-1 agonist that enhances glucose-dependent insulin secretion, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying.

Slideshow: Can Prescription Drugs Lead to Weight Gain?



Exenatide median T max was 2.1 h, mean C max was 211 pg/mL, and mean AUC 0-inf was 1,036 pg•h/mL following subcutaneous administration of exenatide 10 mcg. Following a single dose of exenatide ER, exenatide is released from the microspheres over approximately 10 wk, with an initial period of release followed by a gradual release of exenatide with 2 peaks in plasma at around wk 2 and wk 6 to 7. After 6 to 7 wk, C max was about 300 pg/mL.


Mean apparent Vd of exenatide is 28.3 L and is expected to remain unchanged for exenatide ER.


Predominantly eliminated by glomerular filtration with subsequent proteolytic degradation. Mean Cl is 9.1 L/h. Mean terminal half-life is 2.4 h ( Byetta ). Concentrations are measurable for approximately 10 h postdose ( Byetta ).

Special Populations

Renal Function Impairment

In patients with mild to moderate renal impairment, exposure to exenatide was similar to that of patients with healthy renal function. Exposure to exenatide increased by 3.37-fold in patients with ESRD receiving dialysis. Exenatide ER has not been studied in patients with severe renal impairment or ESRD receiving dialysis. Population pharmacokinetic analysis of renally impaired patients receiving exenatide 2 mg ER indicated there is a 62% and 33% increase in exposure in moderate and mild renal impairment, respectively.

Hepatic Function Impairment

No pharmacokinetic studies have been done; however, because exenatide is cleared primarily by the kidney, hepatic impairment is not expected to affect blood levels.


Age does not influence pharmacokinetic properties of exenatide.


Gender does not influence the distribution and elimination of exenatide.


Race does not influence the pharmacokinetics of exenatide.

Indications and Usage

Adjunctive therapy to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus in multiple clinical settings.


Hypersensitivity to exenatide or any of the product's components.

Exenatide ER

Patients with a personal or family history of medullary thyroid carcinoma; patients with multiple endocrine neoplasia syndrome type 2.

Dosage and Administration

Type 2 Diabetes Mellitus
Adults Bydureon

Subcutaneous 2 mg once every 7 days (weekly). The day of weekly administration can be changed if necessary as long as the last dose was administered 3 or more days before. If a dose is missed, administer it as soon as noticed, provided the next regularly scheduled dose is due at least 3 days later. Thereafter, resume usual dosing schedule of once every 7 days (weekly). If a dose is missed and the next regularly scheduled dose is due 1 or 2 days later, do not administer the missed dose; instead, resume with the next regularly scheduled dose.


Subcutaneous 5 mcg twice daily 1 h before morning and evening meal. May increase to 10 mcg twice daily after 1 mo. If a dose is missed, resume the treatment regimen as prescribed with the next scheduled dose.


Prior treatment with exenatide is not required when initiating exenatide ER therapy. If the decision is made to start exenatide ER in an appropriate patient already taking exenatide, exenatide should be discontinued. Patients changing from exenatide to exenatide ER may experience transient (approximately 2 wk) elevations in blood glucose concentrations.

General Advice

  • Administer as a subcutaneous dose in the thigh, abdomen, or upper arm. Do not administer IV or IM.
  • Exenatide solution is clear and colorless. Do not use if solution is cloudy or discolored or contains particulate matter. Exenatide ER solution is white to off-white and cloudy after suspension. Use provided diluent only if it is clear and free of particulate matter.
  • Exenatide ER must be injected immediately after the powder is suspended in the diluent and transferred to the syringe. Use a different injection site each week when injecting in the same region.
  • Administer exenatide any time within the 60-min period before the morning and evening meals (or before the 2 main meals of the day, approximately 6 or more hours apart. Do not administer exenatide after a meal. Exenatide ER can be administered at any time of day, with or without meals.
  • Do not mix exenatide with insulin.



Refrigerate between 36° and 46°F. Do not freeze. Do not use if frozen. Protect from light. Each single-dose tray can be kept at room temperature not to exceed 77°F for no more than a total of 4 wk.


Refrigerate between 36° and 46°F. After first use, it can be stored at a temperature not exceeding 77°F. Do not freeze. Do not use if exenatide has been frozen. Protect from light. Discard 30 days after first use, even if some drug remains in the pen.

Drug Interactions


Coadministration of repeated doses of exenatide may decrease digoxin C max and delay the T max ; however, the AUC was not changed. Monitor the clinical response of the patient. If an interaction is suspected, adjust the digoxin dose as needed.

Orally administered drugs (eg, antibiotics, oral contraceptives)

The extent and rate of absorption of these agents may be reduced by exenatide. Instruct patients to take at least 1 h before exenatide.

Hypoglycemic agents (eg, meglitinides [eg, repaglinide], sulfonylureas [eg, glimepiride])

The risk of hypoglycemia may be increased. Closely monitor blood glucose concentrations when exenatide is started or stopped in patients receiving other hypoglycemic agents. Reinforce patient instructions for hypoglycemic management, especially in patients receiving a sulfonylurea or insulin.


Lovastatin AUC and C max may be decreased and the T max may be delayed when coadministered with exenatide. Monitor the clinical response of the patient. If an interaction is suspected, adjust the lovastatin dose as needed.


Exenatide may lead to increased INR and possibly increased bleeding when coadministered with warfarin. Monitor INR more frequently after starting or changing the dose of exenatide. Once a stable INR is established, monitor INR at intervals usually recommended for patients taking warfarin.

Adverse Reactions


Headache (8%); decreased appetite, dizziness (1% to less than 2%); somnolence (postmarketing).


Alopecia (postmarketing).


Diarrhea, nausea (11%); constipation (9%); dyspepsia (7%); vomiting (4%); abdominal distention, abdominal pain, acute pancreatitis, dysgeusia, eructation, flatulence, hemorrhagic and necrotizing pancreatitis sometimes resulting in death (postmarketing).


Kidney transplant and kidney transplant dysfunction, renal impairment, worsened chronic or acute renal failure (postmarketing).


Anaphylactic reaction, angioedema, generalized pruritus, macular or papular rash, urticaria (postmarketing).

Lab Tests

Increased serum creatinine (postmarketing).


Injection-site nodule (77%); injection-site reaction (17%).


Hypoglycemia (5%).


Antibody development (49%).



Exenatide ER causes an increased incidence in thyroid C-cell tumors at clinically relevant exposures in rats compared with controls. It is unknown whether exenatide causes thyroid C-cell tumors, including medullary thyroid carcinoma, in humans because human relevance could not be determined by clinical or nonclinical studies. Exenatide ER is contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients with multiple endocrine neoplasia syndrome type 2. Routine serum calcitonin or thyroid ultrasound monitoring is of uncertain value in patients treated with exenatide ER. Counsel patients regarding the risk and symptoms of thyroid tumors.


Monitor glycemic control and for signs and symptoms of pancreatitis.


Category C . According to Briggs' Drugs in Pregnancy and Lactation , avoid use in pregnancy.




Safety and efficacy are not established.


Use with caution.


Serious hypersensitivity reactions (eg, anaphylaxis, angioedema) have been reported.

Renal Function

Do not use in patients with ESRD or severe renal impairment (CrCl less than 30 mL/min); use with caution in patients with renal transplantation or moderate renal impairment (CrCl 30 to 50 mL/min).

GI disease

Use commonly associated with GI adverse reactions. Not recommended for use in patients with severe GI disease.


Anti-exenatide antibodies may develop. No increase in rates or types of adverse reactions, but glycemic response may be attenuated in some patients with high titers.


Acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, has been reported. Discontinue treatment and do not resume if it develops.

Renal effects

Altered renal function, including increased serum creatinine, renal impairment, worsened chronic renal failure, and acute renal failure, sometimes requiring hemodialysis or kidney transplantation, has been reported. Use with caution in patients with risk factors for development of dehydration or renal impairment.



Rapid decline in blood glucose concentration; severe hypoglycemia; severe nausea and vomiting.

Patient Information

  • Advise patients to read the Medication Guide before starting therapy and with each refill.
  • Inform patients of the potential risks and benefits of therapy and of alternative modes of therapy. Also, fully inform patients about self-management practices, including the importance of proper storage, injection technique, timing of dose and doses of concomitant oral drugs, adherence to meal planning, regular physical activity, periodic blood glucose monitoring and HbA 1c testing, recognition and management of hypoglycemia and hyperglycemia, and assessment for diabetes complications.
  • Advise patients to inform their health care provider if they are pregnant or intend to become pregnant.
  • Advise patients that the risk of hypoglycemia is increased when exenatide is used in combination with a sulfonylurea. Therefore, patients receiving exenatide and a sulfonylurea may require a lower dose of the sulfonylurea to reduce the risk of hypoglycemia. Inform patients that it is also possible that the concomitant use with other glucose-independent insulin secretagogues (eg, meglitinides) could increase the risk of hypoglycemia.
  • Advise patients that treatment with exenatide may result in a reduction in appetite, food intake, and/or body weight, and that there is no need to modify the dosing regimen because of such effects. Treatment may also result in nausea, particularly upon initiation of therapy.
  • Inform patients of the potential risk for pancreatitis and associated signs/symptoms.
  • Inform patients treated with exenatide of the potential risk for worsening renal function and about associated signs and symptoms of renal dysfunction.
  • Inform patients that serious hypersensitivity reactions have been reported during postmarketing use of exenatide.
  • Bydureon
  • Inform patients that exenatide ER causes benign and malignant thyroid C-cell tumors in rats and that the human relevance of this finding is unknown. Counsel patients to report symptoms of thyroid tumors (eg, a lump in the neck, hoarseness, dysphagia or dyspnea).
  • Advise patients that each dose of exenatide ER should be administered as a subcutaneous injection at any time on the dosing day, with or without meals. Patients should be informed that the day of once-every-7-days (weekly) administration can be changed if necessary, as long as the last dose was administered 3 or more days before. If a dose is missed, it should be administered as soon as noticed, provided the next regularly scheduled dose is due at least 3 days later. Thereafter, patients can resume their usual once-every-7-days (weekly) dosing schedule. If a dose is missed and the next regularly scheduled dose is due in 1 or 2 days, the patient should not administer the missed dose and instead should resume therapy with the next regularly scheduled dose. Counsel patients to never share an exenatide ER single-dose tray with another person, even if the needle is changed.
  • Inform patients formerly on exenatide who start exenatide ER that they may experience transient elevations in blood glucose concentrations, which generally improve within the first 2 wk after initiation of therapy.
  • Byetta
  • Instruct patients to administer each dose as a subcutaneous injection in the thigh, abdomen, or upper arm at any time within the 60-min period before the morning and evening meals (or before the 2 main meals of the day, approximately 6 or more hours apart). Do not administer exenatide after a meal. If a dose is missed, resume the treatment regimen as prescribed with the next scheduled dose.
  • Advise patients to read the pen user manual before starting therapy and to review it each time the prescription is refilled. Instruct the patient on proper use and storage of the pen, emphasizing how and when to set up a new pen and noting that only 1 setup step is necessary at initial use. Advise patients not to share the pen and needles. Inform patients that pen needles are not included with the pen and must be purchased separately. Advise patients which needle length and gauge to use.
  • Inform patients that the concurrent use with prandial insulin has not been studied and cannot be recommended. When using in combination with insulin, evaluate the dose of insulin. Consider reducing the dose of insulin in patients at risk of hypoglycemia.

Copyright © 2009 Wolters Kluwer Health.