Byetta - Drug Monograph

Introduction

Byetta (exenatide) is an injectable medication used for the management of type 2 diabetes mellitus. It belongs to the class of glucagon-like peptide-1 (GLP-1) receptor agonists and was the first medication in this class approved by the US Food and Drug Administration (FDA) in 2005. Byetta is typically prescribed as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.

Mechanism of Action

Byetta works by mimicking the action of incretin hormones, specifically glucagon-like peptide-1 (GLP-1). It binds to and activates GLP-1 receptors on pancreatic beta cells, leading to glucose-dependent insulin secretion. Additionally, it suppresses glucagon secretion in a glucose-dependent manner, slows gastric emptying, and promotes satiety through central nervous system mechanisms. Unlike native GLP-1, exenatide is resistant to degradation by dipeptidyl peptidase-4 (DPP-4), resulting in an extended duration of action.

Indications

Byetta is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It may be used as monotherapy or in combination with other antidiabetic agents, including metformin, sulfonylureas, thiazolidinediones, or basal insulin. Byetta is not indicated for type 1 diabetes mellitus or diabetic ketoacidosis.

Dosage and Administration

Byetta is administered subcutaneously twice daily within 60 minutes before the morning and evening meals. The initial dose is 5 mcg twice daily, which may be increased to 10 mcg twice daily after one month based on clinical response. The injection sites include the abdomen, thigh, or upper arm. No dosage adjustment is recommended for renal impairment with creatinine clearance >50 mL/min. For patients with creatinine clearance 30-50 mL/min, use with caution. Byetta is contraindicated in patients with severe renal impairment (creatinine clearance <30 mL/min) or end-stage renal disease.

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 renal impairment (creatinine clearance <30 mL/min) or end-stage renal disease

Warnings and Precautions

• Pancreatitis: There have been postmarketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. Discontinue promptly if pancreatitis is suspected.
• Hypoglycemia: Increased risk when used with sulfonylureas. Consider reducing sulfonylurea dose when initiating Byetta.
• Renal impairment: Not recommended in severe impairment; use with caution in moderate impairment.
• Gastrointestinal disease: Use with caution in patients with severe gastrointestinal disease.
• Immunogenicity: Patients may develop anti-exenatide antibodies; in rare cases, antibody titers may affect glycemic control.

Drug Interactions

• Oral medications: Byetta slows gastric emptying and may reduce the rate and extent of absorption of orally administered drugs. Medications with narrow therapeutic windows (e.g., warfarin) should be taken at least 1 hour before Byetta injection.
• Insulin secretagogues: Increased risk of hypoglycemia when coadministered with sulfonylureas. Dose reduction of sulfonylurea may be necessary.
• Warfarin: International Normalized Ratio (INR) monitoring is recommended when initiating or changing Byetta dosage.

Adverse Effects

• Nausea (44%)
• Vomiting (13%)
• Diarrhea (13%)
• Feeling jittery (9%)
• Dizziness (9%)
• Headache (9%)
• Dyspepsia (6%)

• Acute pancreatitis
• Severe hypersensitivity reactions
• Renal impairment or renal failure
• Hypoglycemia (particularly with concomitant sulfonylurea use)

Monitoring Parameters

• Hemoglobin A1c every 3 months until stable, then every 6 months
• Fasting and postprandial glucose regularly
• Renal function at baseline and periodically during treatment
• Signs and symptoms of pancreatitis (abdominal pain, nausea, vomiting)
• Hypoglycemia symptoms, especially when used with insulin secretagogues
• Body weight
• Thyroid nodules (baseline and during treatment)

Patient Education

• Instruct on proper injection technique, site rotation, and timing (within 60 minutes before meals)
• Explain common gastrointestinal side effects, which often diminish over time
• Educate about hypoglycemia recognition and treatment, especially when using with other diabetes medications
• Advise patients to report severe abdominal pain, nausea, or vomiting immediately
• Inform about the importance of regular blood glucose monitoring
• Emphasize that Byetta is not a substitute for insulin in insulin-requiring patients
• Discuss proper storage (refrigerate unused pens; in-use pen may be kept at room temperature)
• Encourage comprehensive diabetes management including diet, exercise, and regular healthcare provider visits

References

1. FDA Prescribing Information: Byetta (exenatide) injection. Revised 2021. 2. Drucker DJ, Nauck MA. 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. Kendall DM, Riddle MC, Rosenstock J, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. 2005;28(5):1083-1091. 4. American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes—2022. Diabetes Care. 2022;45(Supplement_1):S125-S143. 5. Buse JB, Henry RR, Han J, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. 2004;27(11):2628-2635. 6. Fineman MS, Bicsak TA, Shen LZ, et al. Effect of renal impairment on the pharmacokinetics of exenatide. British Journal of Clinical Pharmacology. 2017;84(1):170-180.