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Exenatide: Drug information

Exenatide: Drug information
(For additional information see "Exenatide: Patient drug information" and see "Exenatide: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Risk of thyroid C-cell tumors (Bydureon):

Exenatide extended release (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 (MTC), in humans as the human relevance of exenatide-ER-induced rodent thyroid C-cell tumors has not been determined.

Exenatide ER is contraindicated in patients with a personal or family history of MTC and in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of exenatide ER and inform them of symptoms of thyroid tumors (eg, mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for detection of MTC in patients treated with exenatide ER.

Brand Names: US
  • Bydureon BCise;
  • Bydureon [DSC];
  • Byetta 10 MCG Pen;
  • Byetta 5 MCG Pen
Brand Names: Canada
  • Bydureon [DSC];
  • Byetta 10 MCG Pen [DSC];
  • Byetta 5 MCG Pen [DSC]
Pharmacologic Category
  • Antidiabetic Agent, Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist
Dosing: Adult

Note: Due to lack of additive glycemic benefit, avoid concomitant use with a dipeptidyl peptidase-4 inhibitor (ADA/EASD [Davies 2018]). May require a dose reduction of insulin and/or insulin secretagogues (sulfonylureas, meglitinides) to avoid hypoglycemia.

Diabetes mellitus, type 2, treatment

Diabetes mellitus, type 2, treatment:

Note: May be used as an adjunctive agent or alternative monotherapy for select patients, including those in whom initial therapy with lifestyle intervention and metformin failed, or who cannot take metformin. May be preferred when weight loss is desired and/or in patients with an HbA1c relatively far from goal (eg, HbA1c 9% to 10%) and type 1 diabetes is not likely; use has not been associated with improved or worsened cardiovascular outcomes (ADA 2021; Holman 2017; Wexler 2020).

Immediate release: SUBQ: Initial: 5 mcg twice daily within 60 minutes prior to morning and evening meals (or before the 2 main meals of the day, ≥6 hours apart); may increase to 10 mcg twice daily after 1 month if needed to achieve glycemic goals.

Missed dose: Missed dose should be skipped; resume at the next scheduled dose.

Extended release: SUBQ: 2 mg once weekly without regard to meals. If changing the day of administration is necessary, allow at least 3 days between 2 doses.

Missed dose: Missed dose should be administered as soon as possible if the next scheduled dose is due in ≥3 days; resume usual schedule thereafter. If there are <3 days until next scheduled dose, omit the missed dose and resume administration at the next scheduled weekly dose.

Conversion from immediate release to extended release:Initiate weekly administration of exenatide extended release the day after discontinuing exenatide immediate release. Note: May experience increased blood glucose levels for ~2 to 4 weeks after conversion. Pretreatment with exenatide immediate release is not required when initiating exenatide extended release.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Immediate release:

CrCl ≥30 mL/minute: No dosage adjustment necessary; use caution with initiation of therapy or when increasing the dose in patients with CrCl 30 to 50 mL/minute; monitor for hypovolemia.

CrCl <30 mL/minute: Use is not recommended.

ESRD: Use is not recommended.

Extended release:

eGFR ≥45 mL/minute/1.73 m2: No dosage adjustment necessary; use caution, monitor for hypovolemia.

eGFR 30 to <45 mL/minute/1.73 m2: Use is not recommended per manufacturer's labeling. However, some data have shown similar safety and efficacy in patients with an eGFR 30 to <60 mL/minute/1.73 m2 compared to those with an eGFR ≥60 mL/minute/1.73 m2; use with caution and monitor carefully (Bethel 2020; Guja 2020; Holman 2017).

eGFR <30 mL/minute/1.73 m2: Use is not recommended.

ESRD: Use is not recommended.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, the need for dosage adjustment is unlikely as hepatic dysfunction is not expected to affect exenatide pharmacokinetics.

Dosing: Pediatric

(For additional information see "Exenatide: Pediatric drug information")

Diabetes mellitus, type 2; adjunct to diet and exercise

Diabetes mellitus, type 2; adjunct to diet and exercise: Children ≥10 years and Adolescents: Extended-release injection (Bydureon/Bydureon BCise): SUBQ: 2 mg once weekly without regard to meals.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Children ≥10 years and Adolescents: Extended-release injection:

eGFR ≥45 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling; pharmacokinetic trials in adults report higher exposure; use caution; monitor for hypovolemia.

eGFR <45 mL/minute/1.73 m2: Use is not recommended.

End-stage renal disease: Use is not recommended.

Dosing: Hepatic Impairment: Pediatric

Children ≥10 years and Adolescents: Extended-release injection: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Auto-injector, Subcutaneous:

Bydureon BCise: 2 mg/0.85 mL (0.85 mL)

Pen-injector, Subcutaneous [preservative free]:

Bydureon: 2 mg (1 ea [DSC])

Solution Pen-injector, Subcutaneous:

Byetta 10 MCG Pen: 10 mcg/0.04 mL (2.4 mL) [contains metacresol]

Byetta 5 MCG Pen: 5 mcg/0.02 mL (1.2 mL) [contains metacresol]

Suspension Reconstituted ER, Subcutaneous:

Bydureon: 2 mg (1 ea [DSC])

Generic Equivalent Available: US

No

Dosage Forms Considerations

Bydureon: Extended release formulation

Byetta: Immediate release formulation

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Pen-injector, Subcutaneous:

Bydureon: 2 mg ([DSC])

Solution Pen-injector, Subcutaneous:

Byetta 10 MCG Pen: 10 mcg/0.04 mL ([DSC]) [contains metacresol]

Byetta 5 MCG Pen: 5 mcg/0.02 mL ([DSC]) [contains metacresol]

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Bydureon: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022200s033lbl.pdf#page=36

Bydureon BCise: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/209210s021lbl.pdf#page=33

Byetta: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/021773s046s047lbl.pdf#page=33

Administration: Adult

SUBQ: Administer via SUBQ injection in the upper arm, thigh, or abdomen; rotate injection sites. If using concomitantly with insulin, administer as separate injections (do not mix); may inject in the same body region as insulin, but not adjacent to one another. Do not inject IV or IM.

Immediate release: Use only if clear, colorless, and free of particulate matter. Administer within 60 minutes prior to morning and evening meal (or prior to the 2 main meals of the day, approximately ≥6 hours apart). Set up each new pen before the first use by priming it. See pen user manual for further details. Dial the dose into the dose window before each administration.

Extended release: May administer without regard to meals or time of day. Bydureon and Bydureon BCise are single-dose devices that do not require priming before injection (Romera 2019; manufacturer’s labeling).

Bydureon single-dose tray: Administer immediately after reconstitution in diluent, the mixture should be white to off-white and cloudy. Do not substitute needles or any other components provided with the single-dose tray.

Bydureon Pen: Allow pen to come to room temperature (wait at least 15 minutes after removal from refrigerator) prior to administration. Hold pen by the end with the orange label and tap firmly against palm of hand to mix (may need to tap up to 80 times or more to thoroughly mix); suspension should appear opaque and white to off-white and evenly mixed. Administer immediately after mixing. To ensure full dose is delivered, after insertion of needle press injection button until it clicks and hold for 10 seconds.

Bydureon BCise autoinjector: Allow autoinjector to come to room temperature (wait at least 15 minutes after removal from refrigerator) prior to administration. Shake autoinjector vigorously for at least 15 seconds; suspension should appear opaque and white to off-white and evenly mixed. Administer immediately after mixing. To ensure full dose is delivered, press autoinjector against skin until it clicks and hold for 15 seconds.

Administration: Pediatric

Parenteral: SUBQ: Extended release: Bydureon, Bydureon BCise: Administer via SUBQ injection in the back of the upper arm, thigh, or abdomen; rotate injection sites; may inject in the same body region each week but administer in a different injection site. Do not inject IV or IM. If using concomitantly with insulin, administer as separate injections (do not mix in same syringe); may inject in the same body region as insulin but not adjacent to one another. May administer without regard to meals or time of day. May self-administer with proper training; caregivers should assist pediatric patients. Bydureon and Bydureon BCise are single-dose devices that do not require priming before injection (Romera 2019; manufacturer's labeling).

Bydureon single-dose tray: Administer immediately after reconstitution; the mixture should be white to off-white and cloudy. Do not substitute needles or any other components provided with the single-dose tray.

Bydureon Pen: Allow pen to come to room temperature (wait ≥15 minutes after removal from refrigerator) prior to administration. Hold pen by the end with the orange label and tap firmly against palm of hand to mix; rotate pen every 10 taps (may need to tap 80 times or more to thoroughly mix); suspension should appear opaque and white to off-white and evenly mixed. Administer immediately after mixing; see product labeling for detailed injection instructions. To ensure full dose is delivered, after insertion of needle press, injection button until it clicks and hold for 10 seconds.

Bydureon BCise autoinjector: Allow autoinjector to rest flat and come to room temperature (wait ≥15 minutes after removal from refrigerator) prior to administration. Shake autoinjector vigorously for ≥15 seconds; suspension should appear opaque and white to off-white and evenly mixed and there should no longer be any white along the sides, bottom, or top; may take longer to mix if not stored flat. Administer immediately after mixing. To ensure full dose is delivered, press autoinjector against skin until it clicks and hold for 15 seconds.

Changing day of administration: If changing the day of administration is necessary, allow ≥3 days between 2 doses.

Missed dose: Extended-release injection: Missed dose should be administered as soon as possible if the next scheduled dose is due in ≥3 days; resume usual schedule thereafter. If there are <3 days until next scheduled dose, omit the missed dose and resume administration at the next scheduled weekly dose.

Hazardous Drugs Handling Considerations

This medication is not on the National Institute for Occupational Safety and Health (NIOSH) (2016) list; however, it may meet the criteria for a hazardous drug. Exenatide may cause carcinogenicity, teratogenicity, reproductive toxicity and has a structural or toxicity profile similar to existing hazardous agents.

Note: Prepared/prefilled syringes may be excluded from some hazardous drug handling requirements; assess risk to determine appropriate containment strategy (USP-NF 2018). Refer to institution-specific handling policies and procedures.

Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends double gloving and a protective gown during subcutaneous administration from a prepared/prefilled syringe (NIOSH 2016).

Use: Labeled Indications

Diabetes mellitus, type 2, treatment: As an adjunct to diet and exercise to improve glycemic control in adults (immediate release and extended release) and pediatric patients ≥10 years of age (extended release only) with type 2 diabetes mellitus.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidence rates are reported for monotherapy use.

>10%:

Gastrointestinal: Diarrhea (extended release: 4% to 11%; immediate release: 1% to 2%), nausea (8% to 11%)

Immunologic: Antibody development (antibody titers commonly decrease with continued use, though a small percentage of patients had increased titers; an attenuated glycemic response may be seen with antibody formation)

Local: Injection-site nodule (extended release: autoinjector: 11%; pen: 77%), injection-site reaction (13% to 24%; reactions were more common with extended-release formulations in antibody-positive patients)

1% to 10%:

Endocrine & metabolic: Hypoglycemia (2% to 5%, including severe hypoglycemia)

Gastrointestinal: Constipation (2% to 9%), decreased appetite (immediate release: 1% to 2%), dyspepsia (3% to 7%), gallbladder disease (≤2%; including cholecystitis or cholelithiasis), vomiting (3% to 4%)

Local: Erythema at injection site (extended release: 2%), injection-site pruritus (extended release: 3%)

Nervous system: Dizziness (1% to 3%), headache (4% to 8%)

Postmarketing:

Cardiovascular: Increased heart rate (Robinson 2013), prolongation P-R interval on ECG (Linnebjerg 2011)

Dermatologic: Alopecia, macular eruption, papular rash, pruritus, urticaria

Gastrointestinal: Abdominal distention, abdominal pain, acute pancreatitis, dysgeusia, eructation, flatulence, hemorrhagic pancreatitis, necrotizing pancreatitis

Hematologic & oncologic: Immune thrombocytopenia

Hypersensitivity: Anaphylaxis, angioedema, severe hypersensitivity reaction

Local: Abscess at injection site, cellulitis at injection site, tissue necrosis at injection site

Nervous system: Drowsiness

Renal: Acute kidney injury, exacerbation of renal failure, increased serum creatinine, kidney transplant dysfunction, renal insufficiency

Contraindications

Prior serious hypersensitivity to exenatide or any component of the formulation; history of or family history of medullary thyroid carcinoma (exenatide ER only); patients with multiple endocrine neoplasia syndrome type 2 (exenatide ER only); history of drug-induced immune-mediated thrombocytopenia.

Canadian labeling: Additional contraindications (not in US labeling):

Bydureon: End-stage renal disease (ESRD) or severe renal impairment (CrCl <30 mL/minute) including dialysis patients.

Byetta: Diabetic ketoacidosis, diabetic coma/precoma or type 1 diabetes mellitus; ESRD or severe renal impairment (CrCl <30 mL/minute) including dialysis patients.

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity: Serious hypersensitivity reactions (eg, anaphylaxis, angioedema) have been reported; discontinue therapy in the event of a hypersensitivity reaction. Serious injection-site reactions (eg, abscess, cellulitis, necrosis), with or without subcutaneous nodules have been reported with use. Isolated cases required surgical intervention.

• Gallbladder disease: Cases of cholelithiasis and cholecystitis have been reported; gallbladder studies and further clinical assessment are indicated if cholelithiasis is suspected.

• GI symptoms: Most common reactions are GI related; these symptoms may be dose-related and may decrease in frequency/severity with gradual titration and continued use.

• Pancreatitis: Cases of acute pancreatitis (including hemorrhagic and necrotizing with some fatalities) have been reported; monitor for signs and symptoms of pancreatitis (eg, persistent severe abdominal pain that may radiate to the back, and that may or may not be accompanied by vomiting). Prior to initiating therapy, consider other factors associated with pancreatitis that may be present (eg, hypertriglyceridemia, ethanol abuse, cholelithiasis); it is unknown if exenatide increases the risk for pancreatitis in these patients. If pancreatitis is suspected, discontinue use. Do not resume unless an alternative etiology of pancreatitis is confirmed. Consider alternative antidiabetic therapy in patients with a history of pancreatitis.

• Renal effects: Cases of acute renal failure and chronic renal failure exacerbation, including severe cases requiring hemodialysis or kidney transplantation, have been reported. May cause nausea/vomiting/diarrhea with transient hypovolemia that can worsen renal function. Renal dysfunction was usually reversible with appropriate corrective measures, including discontinuation of exenatide. Risk may be increased in patients receiving concomitant medications affecting renal function and/or hydration status.

• Thrombocytopenia: Serious bleeding (may be fatal) from drug-induced immune-mediated thrombocytopenia has been reported. Discontinue use and do not reinitiate therapy if drug-induced thrombocytopenia is suspected; thrombocytopenia may persist for ~10 weeks after discontinuation of therapy.

• Thyroid tumors: Bydureon: [US Boxed Warning] Thyroid C-cell tumors have developed in animal studies with exenatide ER; it is not known if exenatide ER causes thyroid C-cell tumor, including medullary thyroid carcinoma (MTC) in humans. Patients should be counseled on the potential risk of MTC with the use of exenatide and informed of symptoms of thyroid tumors (eg, neck mass, dysphagia, dyspnea, persistent hoarseness). Use of exenatide ER is contraindicated in patients with a personal or a family history of medullary thyroid cancer and in patients with multiple endocrine neoplasia syndrome type 2 (MEN2). Consultation with an endocrinologist is recommended in patients who develop elevated calcitonin concentrations or have thyroid nodules detected during imaging studies or physical exam; routine monitoring of serum calcitonin or using thyroid ultrasound for early detection of MTC is of unknown value. Cases of MTC in humans have been reported with the GLP-1 agonist, liraglutide.

Disease-related concerns:

• Bariatric surgery:

- Dehydration: Evaluate, correct, and maintain postsurgical fluid requirements and volume status prior to initiating therapy, and closely monitor the patient for the duration of therapy; acute and chronic kidney failure exacerbation may occur. A majority of cases occurred in patients with nausea, vomiting, diarrhea, and/or dehydration. Nausea is common and fluid intake may be more difficult after gastric bypass, sleeve gastrectomy, and gastric band (Mechanick 2020).

- Excessive glucagon-like peptide-1 exposure: Closely monitor for efficacy and assess for signs and symptoms of pancreatitis if therapy is initiated after surgery; gastric bypass and sleeve gastrectomy (but not gastric band) significantly increase endogenous postprandial glucagon-like peptide-1 (GLP-1) concentrations (Korner 2009; Peterli 2012). Administration of exogenous GLP-1 agonists may be redundant to surgery effects.

• GI disease: Not recommended to be used in patients with gastroparesis or severe GI disease due to frequent GI adverse effects associated with use.

• Renal impairment: Use is not recommended in patients with a CrCl <30 mL/minute (exenatide) or <45 mL/minute (exenatide ER) or end-stage renal disease (ESRD). If used in renal transplant recipients, monitor for hypovolemia.

Dosage form specific issues:

• Injection-site reactions: Bydureon: Serious injection-site reactions (eg, abscess, cellulitis, necrosis), with or without subcutaneous nodules, have been reported.

• Multiple dose injection pens: According to the CDC, pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).

Other warnings/precautions:

• Appropriate use: Not for use in patients with type 1 diabetes mellitus or diabetic ketoacidosis.

• Duplicate therapy: Avoid concurrent use of extended-release (weekly) and immediate-release (daily) exenatide formulations.

• Pediatric: Unlike the extended-release formulations (Bydureon, Bydureon BCise), the immediate-release formulation (Byetta) did not show efficacy in the treatment of type 2 diabetes mellitus in pediatric patients 10 to 17 years of age in clinical trials.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Beta-Blockers (Beta1 Selective): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Beta-Blockers (Nonselective): May enhance the hypoglycemic effect of Antidiabetic Agents. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Bortezomib: May enhance the therapeutic effect of Antidiabetic Agents. Bortezomib may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Etilefrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Hormonal Contraceptives: May diminish the therapeutic effect of Exenatide. Exenatide may decrease the serum concentration of Hormonal Contraceptives. Management: Administer oral hormonal contraceptives at least one hour prior to exenatide. Monitor blood glucose more frequently when patients treated with exenatide initiate therapy with a hormonal contraceptive. Increases in exenatide doses may be needed. Risk D: Consider therapy modification

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Insulins: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Insulins. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modification

Liraglutide: May enhance the adverse/toxic effect of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid combination

Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Meglitinides: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Meglitinides. Management: Consider meglitinide dose reductions when used in combination with glucagon-like peptide-1 agonists, particularly when also used with basal insulin. Risk D: Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy

Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Semaglutide: May enhance the adverse/toxic effect of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid combination

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification

Sulfonylureas: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Warfarin: Exenatide may enhance the anticoagulant effect of Warfarin. Risk C: Monitor therapy

Reproductive Considerations

Glucagon-like peptide-1 (GLP-1) receptor agonists are not recommended for patients with type 2 diabetes mellitus planning to become pregnant. Patients who could become pregnant should use effective contraception during therapy. Transition to a preferred therapy should be initiated prior to conception and contraception should be continued until glycemic control is achieved (ADA 2021; Alexopoulos 2019; Egan 2020)

Pregnancy Considerations

Based on in vitro data, exenatide has a low potential to cross the placenta (Hiles 2003).

Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major malformations, stillbirth, and macrosomia. To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2021; Blumer 2013).

Agents other than exenatide are currently recommended to treat diabetes mellitus in pregnancy (ADA 2021).

Breastfeeding Considerations

It is not known if exenatide is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring Parameters

Serum glucose; renal function; volume status; weight; triglycerides; signs/symptoms of pancreatitis; signs/symptoms of gallbladder disease.

HbA1c: Monitor at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; monitor quarterly in patients in whom treatment goals have not been met, or with therapy change. Note: In patients prone to glycemic variability (eg, patients with insulin deficiency), or in patients whose HbA1c is discordant with serum glucose levels or symptoms, consider evaluating HbA1c in combination with blood glucose levels and/or a glucose management indicator (ADA 2021; KDIGO 2020).

Reference Range

Recommendations for glycemic control in patients with diabetes:

Nonpregnant adults (ADA 2021):

HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics). Note: In patients using a continuous glucose monitoring system, a goal of time in range >70% with time below range <4% is recommended and is similar to a goal HbA1c <7%.

Preprandial capillary blood glucose: 80 to 130 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).

Peak postprandial capillary blood glucose (~1 to 2 hours after a meal): <180 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).

Older adults (≥65 years of age) (ADA 2021):

Note: Consider less strict targets in patients who are using insulin and/or insulin secretagogues (sulfonylureas, meglitinides) (ES [LeRoith 2019]).

HbA1c: <7% to7.5% (healthy); <8% to 8.5% (complex/intermediate health). Note: Individualization may be appropriate based on patient and caregiver preferences and/or presence of cognitive impairment. In patients with very complex or poor health (ie, limited remaining life expectancy), consider making therapy decisions based on avoidance of hypoglycemia and symptomatic hyperglycemia rather than HbA1c level.

Preprandial capillary blood glucose: 80 to 130 mg/dL (healthy); 90 to 150 mg/dL (complex/intermediate health); 100 to 180 mg/dL (very complex/poor health).

Bedtime capillary blood glucose: 80 to 180 mg/dL (healthy); 100 to 180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health).

Classification of hypoglycemia (ADA 2021):

Level 1: 54 to 70 mg/dL; hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.

Level 2: <54 mg/dL; threshold for neuroglycopenic symptoms; requires immediate action.

Level 3: Hypoglycemia associated with a severe event characterized by altered mental and/or physical status requiring assistance.

Mechanism of Action

Exenatide is an analog of the hormone incretin (glucagon-like peptide 1 or GLP-1) which increases glucose-dependent insulin secretion, decreases inappropriate glucagon secretion, increases B-cell growth/replication, slows gastric emptying, and decreases food intake. Exenatide administration results in decreases in hemoglobin A1c by approximately 0.5% to 1% (immediate release) or 1.5% to 1.9% (extended release).

Pharmacokinetics

Note: In pediatric patients ≥11 years of age, pharmacokinetic parameters of the extended-release formulation were reported to be similar to adults.

Distribution: Vd: 28.3 L

Metabolism: Minimal systemic metabolism; proteolytic degradation may occur following glomerular filtration

Half-life elimination:

Immediate release (daily) formulation: 2.4 hours

Extended release (weekly) formulation: ~2 weeks

Time to peak, plasma: SubQ:

Immediate release (daily) formulation: 2.1 hours

Extended release (weekly) formulation: Single dose: Initial period of release of surface-bound exenatide is followed by a gradual release from microspheres with peaks at week 2 and week 6 to 7 respectively; with once-weekly dosing steady state is achieved at 6 to 7 weeks (Bydureon) and 10 weeks (Bydureon BCise).

Excretion: Urine (majority of dose)

Pharmacokinetics: Additional Considerations

Altered kidney function: In patients with mild to moderate renal impairment, exposure to exenatide was increased compared with patients with normal renal function.

Pricing: US

Auto-injector (Bydureon BCise Subcutaneous)

2MG/0.85ML (per 0.85 mL): $233.98

Solution Pen-injector (Byetta 10 MCG Pen Subcutaneous)

10 mcg/0.04 mL (per mL): $400.58

Solution Pen-injector (Byetta 5 MCG Pen Subcutaneous)

5 mcg/0.02 mL (per mL): $801.16

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Baietta (CR, DO, GT, HN, MX, NI, PA, SV);
  • Bydureon (AE, AT, AU, BE, BH, CH, CR, CZ, DE, DK, DO, EG, ES, GB, GT, HN, IE, IL, JP, KR, LB, LT, LU, LV, MT, MX, NI, NL, NO, NZ, PA, PL, SE, SG, SI, SK, SV);
  • Bydureon BCise (AU);
  • Byetta (AE, AT, AU, BB, BE, BG, BH, CH, CL, CN, CO, CY, DE, DK, EC, EE, EG, ES, FI, FR, GB, GR, HK, HU, IE, IL, IS, IT, JO, JP, KR, KW, LT, LU, LV, MT, MY, NL, NO, NZ, PH, PK, PL, PT, QA, RO, RU, SA, SE, SI, SK, TH, TR, TW, ZA)


For country code abbreviations (show table)
  1. <800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 40-NF 35). Rockville, MD: United States Pharmacopeia Convention; 2018:84-103.
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  4. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 190: Gestational diabetes mellitus. Obstet Gynecol. 2018;131(2):e49-e64. [PubMed 29370047]
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  6. Bethel MA, Mentz RJ, Merrill P, et al. Microvascular and cardiovascular outcomes according to renal function in patients treated with once-weekly exenatide: insights from the EXSCEL trial. Diabetes Care. 2020;43(2):446-452. doi:10.2337/dc19-1065 [PubMed 31757838]
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  9. Bydureon (exenatide) [product monograph]. Mississauga, Ontario, Canada: AstraZeneca Canada Inc; January 2020.
  10. Bydureon (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; July 2022.
  11. Bydureon (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; June 2022.
  12. Bydureon BCise (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; July 2021.
  13. Bydureon BCise (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; June 2022.
  14. Bydureon BCise (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; December 2020.
  15. Byetta (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; June 2021.
  16. Byetta (exenatide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; June 2022.
  17. Byetta (exenatide) injection [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; November 2021.
  18. Byetta (exenatide) [product monograph]. Mississauga, Ontario, Canada: AstraZeneca Canada Inc; December 2019.
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