FOR ADULTS WITH TYPE 2 DIABETES UNCONTROLLED ON ONE OR MORE ORAL ANTIDIABETIC AGENTS IN ADDITION TO DIET AND EXERCISE

WHEN CONSIDERING AN INJECTABLE,

ONCE-WEEKLY

BYDUREON FIRST*

TO HELP PATIENTS GET CONSISTENT CONTROL

*The AACE Comprehensive Algorithm supports the addition of GLP-1 RAs before basal insulin based on important considerations: for patients1 with entry A1C ≥7.5% or >9% with no symptoms.1

IMPORTANT SAFETY INFORMATION

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IMPORTANT SAFETY INFORMATION

WARNING: RISK OF THYROID C-CELL TUMORS

  • Exenatide extended-release causes an increased incidence in thyroid C-cell tumors at clinically relevant exposures in rats compared to controls. It is unknown whether BYDUREON or BYDUREON BCise cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of exenatide extended-release-induced rodent thyroid C-cell tumors has not been determined

  • BYDUREON and BYDUREON BCise are contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with the use of BYDUREON or BYDUREON BCise 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 BYDUREON or BYDUREON BCise

CONTRAINDICATIONS

  • Personal or family history of MTC, patients with MEN 2

  • Prior serious hypersensitivity reactions to exenatide or product components

WARNINGS AND PRECAUTIONS

  • Acute Pancreatitis including fatal and non-fatal hemorrhagic or necrotizing pancreatitis has been reported. After initiation, observe patients carefully for symptoms of pancreatitis. If suspected, discontinue promptly and do not restart if confirmed. Consider other antidiabetic therapies in patients with a history of pancreatitis

  • Hypoglycemia Risk of hypoglycemia is increased when exenatide is coadministered with insulin or insulin secretagogues. Consider lowering the dose of these agents when coadministered with BYDUREON or BYDUREON BCise

  • Acute Kidney Injury and Impairment of Renal Function Altered renal function, including increased serum creatinine, renal impairment, worsened chronic renal failure, and acute renal failure, sometimes requiring hemodialysis and kidney transplantation have been reported. Not recommended in patients with severe renal impairment or end-stage renal disease. Use caution in patients with renal transplantation or moderate renal impairment

  • Gastrointestinal Disease Because exenatide is commonly associated with gastrointestinal adverse reactions, not recommended in patients with severe gastrointestinal disease (eg, gastroparesis)

  • Immunogenicity Patients may develop antibodies to exenatide. Patients with higher titer antibodies may have an attenuated HbA1c response. In clinical trials, attenuated glycemic response was associated with BYDUREON- or BYDUREON BCise-treated patients. If worsening of or failure to achieve adequate glycemic control occurs, consider alternative antidiabetic therapy

  • Hypersensitivity Reports of serious hypersensitivity reactions (eg, anaphylaxis and angioedema). If this occurs, patients should discontinue BYDUREON or BYDUREON BCise and promptly seek medical advice

  • Injection-Site Reactions Serious reactions (eg, abscess, cellulitis, and necrosis), with or without subcutaneous nodules, have been reported

  • Macrovascular Outcomes No clinical studies establishing conclusive evidence of macrovascular risk reduction with exenatide

ADVERSE REACTIONS

  • Most common (≥5%) and occurring more frequently than comparator in BYDUREON clinical trials: nausea (16.9%), diarrhea (12.7%), headache (8.0%), vomiting (6.8%), constipation (5.9%), injection-site pruritus (5.9%), injection-site nodule (5.3%), dyspepsia (5.1%)

  • Most common (≥5%) in BYDUREON BCise clinical trials: injection-site nodule (10.5%), nausea (8.2%)

DRUG INTERACTIONS

  • Oral Medications BYDUREON and BYDUREON BCise slow gastric emptying and may reduce the rate of absorption of orally administered drugs

  • Warfarin Increased international normalized ratio (INR) sometimes associated with bleeding has been reported with concomitant use of exenatide with warfarin. Monitor INR frequently until stable upon initiation of BYDUREON or BYDUREON BCise

PREGNANCY

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

INDICATION AND LIMITATIONS OF USE

BYDUREON and BYDUREON BCise are both indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

  • Not recommended as first-line therapy for patients inadequately controlled on diet and exercise

  • Not a substitute for insulin. Should not be used to treat type 1 diabetes or diabetic ketoacidosis

  • Not recommended for use with insulin

  • Do not coadminister with other exenatide-containing products

  • Not studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis

Please click here for Prescribing Information and Medication Guide for BYDUREON BCise.

Please click here for Prescribing Information and Medication Guide for BYDUREON.

You may report side effects related to AstraZeneca products by clicking here.

Abbreviations: GF, glucose fluctuations; GLP-1 RA, glucagon-like peptide-1 receptor agonist.

References:

  1. DeYoung MB, MacConell L, Sarin V, et al. Diabetes Technol Ther. 2011;13(11):1145-1154.

  2. Drucker DJ, Buse JB, Taylor K, et al; for the DURATION-1 Study Group. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet. 2008;372(9645):1240-1250.

  3. BYDUREON [package insert]. AstraZeneca Pharmaceuticals, LP: Wilmington, DE; 2017.

  4. Data on file, REF-19541, AstraZeneca Pharmaceuticals, LP.

  5. BYDUREON BCise ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

Abbreviation: GLP-1 RA, glucagon-like peptide-1 receptor agonist.

References:

  1. BYDUREON BCise ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

  2. Data on file, REF-14053, AstraZeneca Pharmaceuticals, LP.

Abbreviations: BID, twice daily; BL, baseline; ITT, intent-to-treat; QD, once daily; QW, once weekly; SU, sulfonylurea; TZD, thiazolidinedione.

References:

  1. BYDUREON BCise ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

  2. Wysham CH, Rosenstock J, Vetter ML, et al. Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes [published online ahead of print July 7, 2017]. Diabetes Obes Metab. http:// dx.doi.org/10.1111/dom.13056. Accessed October 18, 2017.

  3. Gadde KM, Vetter ML, Iqbal N, et al. DURATION-NEO-2 study investigators. Efficacy and safety of autoinjected exenatide once-weekly suspension versus sitagliptin or placebo with metformin in patients with type 2 diabetes: the DURATION-NEO-2 randomized clinical study. Diabetes Obes Metab. 2017;19(7):979-988.

Abbreviation: PK, pharmacokinetic.

References:

  1. BYDUREON BCise ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

  2. Data on file, REF-19541, AstraZeneca Pharmaceuticals, LP.

  3. Wysham CH, Rosenstock J, Vetter ML, et al. Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes [published online ahead of print July 7, 2017]. Diabetes Obes Metab. http:// dx.doi.org/10.1111/dom.13056. Accessed October 18, 2017.

  4. DeYoung MB, MacConell L, Sarin V, et al. Encapsulation of exenatide in poly-(D,L-lactide-co-glycolide) microspheres produced an investigational long-acting once-weekly formulation for type 2 diabetes. Diabetes Technol Ther. 2011;13(11):1145-1154.

Abbreviations: BID, twice daily; ITT, intent-to-treat; QW, once weekly.

References:

  1. BYDUREON BCise ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

  2. Data on file, REF-7842, AstraZeneca Pharmaceuticals, LP.

  3. Drucker DJ, Buse JB, Taylor K, et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet. 2008;372:1240-1250.

  4. Wysham CH, Philis-Tsimikas A, Klein EJ, et al. DURATION-1 extension in patients with T2D:efficacy and tolerability of exenatide once weekly (QW) over 7 years (abstract 1041-P) Diabetes. 2016;65(Suppl 1):A221–A360.

References:

  1. BYDUREON BCise ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

  2. DeYoung MB, MacConell L, Sarin V, et al. Diabetes Technol Ther. 2011;13(11):1145-1154.

Abbreviations: AACE, American Association of Clinical Endocrinologists; GF, glucose fluctuations; GLP-1 RA, glucagon-like peptide-1 receptor agonist.

Reference:

  1. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2017 executive summary. Endocr Pract. 2017;23(2):207-238.

Abbreviations: FPG, fasting plasma glucose; GF, glucose fluctuations; GLP-1 RA, glucagon-like peptide-1 receptor agonist; IG, insulin glargine; IU=international units; INITIATE, initiate insulin by aggressive titration and education; IU, international unit; LS, least squares; MET, metformin; mITT, modified intent-to-treat; SU, sulfonylurea.

References:

  1. Diamant M, Van Gaal L, Guerci B, et al. Exenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3): 3-year results of an open-label randomised trial. Lancet Diabetes Endocrinol. 2014;2(6):464-473.

  2. Data on file, REF-5090, AstraZeneca Pharmaceuticals, LP.

  3. Diamant M, Van Gaal L, Stranks S, et al. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet. 2010;375(9733):2234-2243.

  4. Yki-Järvinen H, Juurinen L, Alvarsson M, et al. Initiate Insulin by Aggressive Titration and Education (INITIATE): a randomized study to compare initiation of insulin combination therapy in type 2 diabetic patients individually and in groups. Diabetes Care. 2007;30(6):1364-1369.

  5. Bergenstal RM, Wysham C, MacConell L, et al; for the DURATION-2 Study Group. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet. 2010;376(9739):431-439.

  6. Russell-Jones D, Cuddihy RM, Hanefeld M, et al; on behalf of the DURATION-4 Study Group. Efficacy and safety of exenatide once weekly versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug-naive patients with type 2 diabetes (DURATION-4): a 26-week double-blind study. Diabetes Care. 2012;35(2):252-258.

  7. Blevins T, Pullman J, Malloy J, et al. DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011;96(5):1301-1310.

  8. Buse JB, Nauck M, Forst T, et al. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Lancet. 2013;381(9861):117-124.

  9. Data on file, REF-4935, AstraZeneca Pharmaceuticals, LP.

  10. Data on file, REF-4940, AstraZeneca Pharmaceuticals, LP.

  11. Data on file, REF-4951, AstraZeneca Pharmaceuticals, LP.

  12. Supplementary Appendix to: Diamant M, Van Gaal L, Guerci B, et al. Exenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3): 3-year results of an open label randomised trial. Lancet Diabetes Endocrinol. 2014:1-11.

References:

  1. Frias JP, Nakhle S, Ruggles JA, et al. Exenatide once weekly improved 24-hour glucose control and reduced glycaemic variability in metformin-treated participants with type 2 diabetes: a randomized, placebo-controlled trial. [published online ahead of print August 16, 2016]. Diabetes Obes Metab. doi:10.1111/dom.12763.

  2. Data on file, REF-5039, AstraZeneca Pharmaceuticals, LP.

Abbreviations: GF, glucose fluctuations; GLP-1 RA, glucagon-like peptide-1 receptor agonist; PK, pharmacokinetic.

References:

  1. Drucker DJ, Buse JB, Taylor K, et al; for the DURATION-1 Study Group. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet. 2008;372(9645):1240-1250.

  2. DeYoung MB, MacConell L, Sarin V, et al. Encapsulation of exenatide in poly-(D,L-lactideco-glycolide) microspheres produced an investigational long-acting once-weekly formulation for type 2 diabetes. Diabetes Technol Ther. 2011;13(11):1145-1154.

Abbreviations: GF, glucose fluctuations; IU, International unit; mITT, modified intent-to-treat; QW, once weekly.

References:

  1. Diamant M, Van Gaal L, Guerci B, et al. Exenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3): 3-year results of an open-label randomised trial. Lancet Diabetes Endocrinol. 2014;2(6):464-473.

  2. Data on file, REF-5090, AstraZeneca Pharmaceuticals, LP.

  3. BYDUREON ([exenatide extended-release] injectable suspension) [prescribing information]. AstraZeneca Pharmaceuticals, LP: Wilmington, DE; 2017.

  4. Data on file, REF-4977, AstraZeneca Pharmaceuticals, LP.

  5. Data on file, REF-7842, AstraZeneca Pharmaceuticals, LP.

  6. Drucker DJ, Buse JB, Taylor K, et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet. 2008;372:1240-1250.

  7. Wysham CH, Philis-Tsimikas A, Klein EJ, et al. DURATION-1 extension in patients with T2D: efficacy and tolerability of exenatide once weekly (QW) over 7 years (abstract 1041-P) Diabetes. 2016;65(Suppl 1):A221–A360.

Reference:

  1. BYDUREON [package insert]. AstraZeneca Pharmaceuticals, LP: Wilmington, DE; 2017.

Reference:

  1. BYDUREON BCise ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

Abbreviation: FDA, US Food and Drug Administration.

References:

  1. BYDUREON [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

  2. DeYoung MB, MacConell L, Sarin V, Trautmann M, Herbert P. Diabetes Technol Ther. 2011;13(11):1145-1154.

  3. Data on file, AstraZeneca Pharmaceuticals LP, REF-2991504.

References:

  1. BYDUREON BCise ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

  2. DeYoung MB, MacConell L, Sarin V, Trautmann M, Herbert, P. Diabetes Technol Ther. 2011;13(11):1145-1154.

References:

  1. BYDUREON BCise ([exenatide extended-release] injectable suspension) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.

  2. Data on file, REF-14053, AstraZeneca Pharmaceuticals, LP.