Version July 2025
The FDA has been evaluating reports of suicidal thoughts or actions in patients treated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs). A preliminary evaluation has not found evidence that the use of these medicines causes suicidal thoughts or actions, but the FDA is continuing to investigate this issue. Patients should not stop taking GLP-1 RAs without consulting their health care provider. Health care providers should monitor for and advise patients using GLP-1 RAs to report new or worsening depression, suicidal thoughts, or any unusual changes in mood or behavior.
Further information may be found at https://www.fda.gov/drugs/drug-safety-and-availability/update-fdas-ongoing-evaluation-reports-suicidal-thoughts-or-actions-patients-taking-certain-type.
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.
Dosage guidance:
Clinical considerations: May require a dose reduction of insulin and/or insulin secretagogues (sulfonylureas, meglitinides) to avoid hypoglycemia.
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 (Ref). Due to lack of additive glycemic benefit, avoid concomitant use with a dipeptidyl peptidase-4 inhibitor (Ref).
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.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
Immediate release: SUBQ:
CrCl ≥30 mL/minute: No dosage adjustment necessary. Use caution when initiating or escalating doses, especially in patients with CrCl 30 to 50 mL/minute. New onset or worsening of existing kidney impairment has been reported; risk may be increased in patients experiencing volume depletion from GI losses (eg, vomiting, diarrhea). Monitor for hypovolemia (Ref).
CrCl <30 mL/minute: Use is not recommended (Ref).
Extended release: SUBQ:
eGFR ≥45 mL/minute/1.73 m2: No dosage adjustment necessary. Use caution when initiating or escalating doses. New onset or worsening of existing kidney impairment has been reported; risk may be increased in patients experiencing volume depletion from GI losses (eg, vomiting, diarrhea). Monitor for hypovolemia (Ref).
eGFR 30 to <45 mL/minute/1.73 m2: Use is not recommended per manufacturer's labeling. However, multiple trials have included patients with eGFRs as low as 30 mL/minute/1.73 m2 (Ref), and similar safety outcomes and impact on efficacy markers (ie, HbA1c, weight) have been reported in patients with moderate kidney disease (eGFR 30 to 60 mL/minute/1.73 m2) compared to those with higher eGFRs (Ref). Use with caution and monitor closely for worsening of kidney function and/or hypovolemia.
eGFR <30 mL/minute/1.73 m2: Use is not recommended (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
SUBQ: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzable due to large molecular weight (Ref):
SUBQ: Use is not recommended due to pharmacokinetic studies demonstrating a >3-fold increase in exenatide exposure in patients with end-stage kidney disease (ESKD) and increased risk of GI adverse effects (Ref).
Peritoneal dialysis: Unlikely to be significantly dialyzable due to large molecular weight (Ref):
SUBQ: Use is not recommended due to pharmacokinetic studies demonstrating a >3-fold increase in exenatide exposure in patients with ESKD and increased risk of GI adverse effects (Ref).
CRRT: SUBQ: Avoid use (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): SUBQ: Avoid use (Ref).
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.
Refer to adult dosing.
(For additional information see "Exenatide: Pediatric drug information")
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.
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.
Children ≥10 years and Adolescents: Extended-release injection: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
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 reaction (including abscess at injection site, bruising at injection site, cellulitis at injection site, erythema at injection site, hematoma at injection site, injection-site nodule, injection-site pruritus, tissue necrosis at injection site)
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%)
Nervous system: Dizziness (1% to 3%), headache (4% to 8%)
Frequency not defined: Gastrointestinal: Delayed gastric emptying
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, intestinal obstruction, necrotizing pancreatitis
Hematologic & oncologic: Immune thrombocytopenia
Hypersensitivity: Anaphylaxis, angioedema, severe hypersensitivity reaction
Nervous system: Drowsiness
Renal: Acute kidney injury, exacerbation of renal failure, increased serum creatinine, kidney impairment, kidney transplant dysfunction
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.
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 kidney failure and chronic kidney failure exacerbation, including severe cases requiring hemodialysis or kidney transplantation, have been reported. May cause nausea/vomiting/diarrhea with transient hypovolemia that can worsen kidney function. Kidney dysfunction was usually reversible with appropriate corrective measures, including discontinuation of exenatide. Risk may be increased in patients receiving concomitant medications affecting kidney 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: According to the manufacturer’s labeling, use is not recommended in patients with a CrCl <30 mL/minute (IR exenatide), eGFR <45 mL/minute/1.73 m2 (ER exenatide), or end-stage kidney disease. If used in kidney 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.
• Surgical and endoscopic procedures: Use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has been associated with elevated residual gastric contents, which may increase the risk for adverse events during anesthesia and deep sedation (including aspiration) (Kobori 2023; Marroquin-Harris 2023; Silveira 2023). In some studies, delayed gastric emptying induced by GLP-1 RAs returned to baseline after 8 to 12 weeks of continuous therapy; therefore, risk may be higher in patients who recently initiated therapy or who use GLP-1 RAs intermittently (Raven 2024; van Zuylen 2024). Although the American Society of Anesthesiologists has suggested holding GLP-1 RAs prior to planned procedures requiring general anesthesia, the risks and benefits of this approach have not been evaluated (AGA [Hashash 2024]; ASA [Joshi 2023]). For example, in patients using GLP-1 RAs for glycemic control, holding the medication may result in perioperative hyperglycemia and increase the risk of adverse postoperative outcomes (AGA [Hashash 2024]; van Zuylen 2024). Individualize the decision to hold the GLP-1 RA based on patient-specific factors such as the indication (eg, glycemic control vs weight management), duration and frequency of therapy, presence of adverse GI symptoms, and concomitant medications that may slow gastric emptying (eg, opioids, proton pump inhibitors); may consider additional preoperative interventions (eg, clear liquid diet, full stomach precautions, gastric ultrasound) on a case-by-case basis to reduce risk (ASA [Hashash 2024]; Marroquin-Harris 2023; Raven 2024; van Zuylen 2024). Refer also to institutional protocols.
Bydureon: Extended release formulation
Byetta: Immediate release formulation
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 [DSC])
Solution Pen-injector, Subcutaneous:
Byetta 10 MCG Pen: 10 mcg/0.04 mL (2.4 mL [DSC]) [contains metacresol]
Byetta 5 MCG Pen: 5 mcg/0.02 mL (1.2 mL [DSC]) [contains metacresol]
Generic: 10 mcg/0.04 mL (2.4 mL)
May be product dependent
Solution Pen-injector (Exenatide Subcutaneous)
10 mcg/0.04 mL (per mL): $403.73
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.
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]
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 (Ref).
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.
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 (Ref).
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 agent (NIOSH 2024 [table 2]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
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/2022/022200s034lbl.pdf#page=37
Bydureon BCise: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/209210s022lbl.pdf
Byetta: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/021773s046s047lbl.pdf#page=33
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.
None known.
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
Alectinib: Glucagon-Like Peptide-1 Agonists may decrease serum concentration of Alectinib. Risk C: Monitor
Alpha-Lipoic Acid: May increase hypoglycemic effects of Antidiabetic Agents. Risk C: Monitor
Androgens: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Beta-Blockers (Beta1 Selective): May increase adverse/toxic effects of Antidiabetic Agents. Specifically, beta-blockers may mask the hypoglycemic symptoms of antidiabetic agents. Risk C: Monitor
Beta-Blockers (Nonselective): May increase hypoglycemic effects of Antidiabetic Agents. Beta-Blockers (Nonselective) may increase adverse/toxic effects of Antidiabetic Agents. Specifically, beta-blockers may mask the hypoglycemic symptoms of antidiabetic agents. Risk C: Monitor
Bortezomib: May increase therapeutic effects of Antidiabetic Agents. Bortezomib may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Direct Acting Antiviral Agents (HCV): May increase hypoglycemic effects of Antidiabetic Agents. Risk C: Monitor
Etilefrine: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Guanethidine: May increase hypoglycemic effects of Antidiabetic Agents. Risk C: Monitor
Hormonal Contraceptives: May decrease therapeutic effects of Exenatide. Exenatide may decrease 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 decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Hypoglycemia-Associated Agents: Antidiabetic Agents may increase hypoglycemic effects of Hypoglycemia-Associated Agents. Risk C: Monitor
Insulin: Glucagon-Like Peptide-1 Agonists may increase hypoglycemic effects of Insulin. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Monitor patients for hypoglycemia. Risk D: Consider Therapy Modification
Liraglutide: May increase adverse/toxic effects of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid
Maitake: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Meglitinides: Glucagon-Like Peptide-1 Agonists may increase hypoglycemic effects 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 increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Pegvisomant: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Prothionamide: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Quinolones: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Quinolones may decrease therapeutic effects 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
Reproterol: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Ritodrine: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Salicylates: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Selective Serotonin Reuptake Inhibitor: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Semaglutide: May increase adverse/toxic effects of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid
Sincalide: Drugs that Affect Gallbladder Function may decrease therapeutic effects 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 increase hypoglycemic effects 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 decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Tirzepatide: May increase adverse/toxic effects of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid
Warfarin: Exenatide may increase anticoagulant effects of Warfarin. Risk C: Monitor
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 2024; Alexopoulos 2019; Egan 2020).
GLP-1 receptor agonists including exenatide have been evaluated to manage metabolic aspects of polycystic ovary syndrome (PCOS), including decreasing weight and improving fertility (Goldberg 2024; Hu 2023; Jensterle 2022; Ye 2023; Zhou 2023). However, until additional data are available, use in patients with PCOS to improve reproductive outcomes should be limited to research settings (Teede 2024). Note: Exenatide is not approved for weight loss.
Based on in vitro data, exenatide has a low potential to cross the placenta (Hiles 2003).
Outcome data following exposure to glucagon-like peptide-1 receptor agonists, including exenatide during pregnancy, are limited (Cesta 2024; Dao 2024; Doğan 2023).
Poorly controlled diabetes during pregnancy is 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 2024).
Agents other than exenatide are currently recommended to treat diabetes mellitus during pregnancy (ADA 2024).
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.
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 2023; KDIGO 2020).
Recommendations for glycemic control in patients with diabetes:
Nonpregnant adults (AACE [Samson 2023], ADA 2023):
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 (SI: 4.4 to 7.2 mmol/L) (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 (SI: <10 mmol/L) (more or less stringent goals may be appropriate based on patient-specific characteristics).
Older adults (≥65 years of age) (ADA 2023):
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% (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 (SI: 4.4 to 7.2 mmol/L) (healthy); 90 to 150 mg/dL (SI: 5 to 8.3 mmol/L) (complex/intermediate health); 100 to 180 mg/dL (SI: 5.6 to 10 mmol/L) (very complex/poor health).
Bedtime capillary blood glucose: 80 to 180 mg/dL (SI: 4.4 to 10 mmol/L) (healthy); 100 to 180 mg/dL (SI: 5.6 to 10 mmol/L) (complex/intermediate health); 110 to 200 mg/dL (SI: 6.1 to 11.1 mmol/L) (very complex/poor health).
Classification of hypoglycemia (ADA 2023):
Level 1: 54 to 70 mg/dL (SI: 3 to 3.9 mmol/L); hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.
Level 2: <54 mg/dL (SI: <3 mmol/L); 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.
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).
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)
Altered kidney function: In patients with mild to moderate kidney impairment, exposure to exenatide was increased compared with patients with normal kidney function. In a single-dose (immediate release) study of subjects with end-stage kidney disease receiving dialysis, mean exenatide exposure increased by 3.37-fold compared to that of subjects with normal kidney function (Linnebjerg 2007; manufacturer’s labeling).
