Bydureon - Drug Monograph

Introduction

Bydureon (exenatide extended-release) is a glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes mellitus. It represents the first once-weekly injectable medication in its class, offering improved convenience compared to daily GLP-1 agonists. Bydureon works by enhancing glucose-dependent insulin secretion, suppressing inappropriate glucagon secretion, and slowing gastric emptying.

Mechanism of Action

Bydureon exerts its glucose-lowering effects through multiple mechanisms:

• GLP-1 receptor agonism: Bydureon binds to and activates GLP-1 receptors on pancreatic beta cells, stimulating glucose-dependent insulin secretion
• Glucagon suppression: Reduces inappropriate postprandial glucagon secretion from pancreatic alpha cells
• Gastric emptying: Slows gastric emptying, which helps reduce postprandial glucose excursions
• Appetite regulation: Acts on central nervous system receptors to promote satiety and reduce food intake

The extended-release formulation utilizes poly(D,L-lactide-co-glycolide) microspheres that gradually release exenatide over several weeks following subcutaneous administration.

Indications

Bydureon is FDA-approved for:

• Improvement of glycemic control in adults with type 2 diabetes mellitus as an adjunct to diet and exercise
• May be used as monotherapy or in combination with other antidiabetic agents including metformin, sulfonylureas, thiazolidinediones, or insulin (basal insulin only)

Dosage and Administration

• Administer at any time of day, with or without meals
• Injection sites: abdomen, thigh, or back of upper arm
• Rotate injection sites to prevent lipodystrophy
• If a dose is missed, administer as soon as possible within 3 days of the missed dose; if more than 3 days have passed, wait until the next regularly scheduled dose

• Renal impairment: Not recommended in patients with severe renal impairment (CrCl <30 mL/min) or end-stage renal disease
• Hepatic impairment: No dosage adjustment necessary
• Elderly: No dosage adjustment required, but consider increased sensitivity
• Pediatric: Safety and effectiveness not established

Pharmacokinetics

Contraindications

• History of hypersensitivity to exenatide or any product components
• Personal or family history of medullary thyroid carcinoma
• Patients with Multiple Endocrine Neoplasia syndrome type 2
• Severe gastrointestinal disease, including gastroparesis

Warnings and Precautions

• Pancreatitis: Discontinue promptly if pancreatitis is suspected
• Hypoglycemia: Increased risk when used with sulfonylureas or insulin; may require dose reduction of these agents
• Renal impairment: Use caution in renal transplantation; not recommended in severe renal impairment
• Gastrointestinal effects: Nausea, vomiting, and diarrhea may occur; may lead to dehydration and worsened renal function
• Immunogenicity: Low potential for antibody formation that may affect efficacy
• Macrovascular outcomes: No established evidence of reduced macrovascular risk

Drug Interactions

• Oral medications: May decrease absorption of orally administered drugs due to slowed gastric emptying (monitor drugs with narrow therapeutic index)
• Warfarin: Increased INR reported in postmarketing experience (monitor INR more frequently)
• Sulfonylureas: Increased risk of hypoglycemia (consider reducing sulfonylurea dose)
• Insulin: Increased risk of hypoglycemia (consider reducing insulin dose)
• Drugs primarily excreted renally: Use caution with drugs that have narrow therapeutic windows

Adverse Effects

• Nausea (14%)
• Diarrhea (9%)
• Vomiting (7%)
• Injection site reactions (7%)
• Constipation (6%)
• Headache (6%)

• Pancreatitis (including fatal and non-fatal hemorrhagic or necrotizing)
• Hypersensitivity reactions
• Severe gastrointestinal disease
• Acute kidney injury
• Hypoglycemia (when used with insulin secretagogues or insulin)

Monitoring Parameters

• HbA1c, fasting plasma glucose
• Renal function (serum creatinine, eGFR)
• Thyroid examination (palpation)
• Weight and BMI
• Cardiovascular risk assessment

• HbA1c every 3 months until stable, then every 6 months
• Fasting plasma glucose regularly
• Renal function annually or as clinically indicated
• Signs/symptoms of pancreatitis (nausea, vomiting, abdominal pain)
• Hypoglycemia symptoms, especially when used with insulin or sulfonylureas
• Injection sites for reactions
• Thyroid nodules (annual palpation)

Patient Education

• Administer once weekly on the same day each week
• Rotate injection sites to prevent skin reactions
• Proper injection technique and storage requirements
• Recognize symptoms of hypoglycemia and appropriate management
• Report severe abdominal pain, nausea, or vomiting (possible pancreatitis)
• Inform all healthcare providers about Bydureon use
• Do not share pens or needles with others
• Discontinue and seek medical attention for allergic reactions
• Potential for weight loss as a beneficial side effect
• Importance of continued diet and exercise regimen

References

1. FDA Prescribing Information: Bydureon (exenatide extended-release). Updated 2023. 2. Drucker DJ, et al. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006;368(9548):1696-1705. 3. Buse JB, 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. 4. Diamant M, 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. 5. American Diabetes Association. Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S1-S291. 6. Garber AJ, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm. Endocr Pract. 2023;29(1):1-27.