Treating Type 2 Diabetes with BYETTA

GLP-1 receptor agonists, such as BYETTA, are included in the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) consensus treatment algorithm.¹

• After lifestyle interventions and metformin fail to achieve or sustain the A1C target of <7%, another medication should be added.
• When hypoglycemia is a concern and weight loss is needed, BYETTA may be considered. BYETTA is not indicated for the management of obesity, and weight change was a secondary endpoint in clinical trials.

ADA/EASD Consensus Algorithm for the Management of Type 2 Diabetes¹

Reinforce lifestyle interventions at every visit. Check A1C every 3 months until A1C is <7% and then at least every 6 months. The interventions should be changed if A1C is ≥7%.

Summary of the tier 1 and tier 2 algorithms¹

Tier 1: These interventions represent the best-established and most effective and cost-effective therapeutic strategy for achieving the target glycemic goals.

Step 1: Lifestyle intervention should be initiated as a first step because of the numerous short- and long-term benefits that accrue from exercise and weight loss. Metformin should be initiated concurrently because of its glycemic effects, absence of weight gain or hypoglycemia, tolerability, and low cost.

Step 2: Another medication should be added to achieve glycemic goals if step 1 fails.

Step 3: Insulin therapy should be started or intensified if glycemic goals have not been reached.

Tier 2: In selected clinical settings, the second-tier algorithm may be considered.

When hypoglycemia is particularly undesirable, the addition of a GLP-1 agonist or pioglitazone to step 1 may be considered. If promotion of weight loss is a major consideration and the A1C level is close to target (<8%), a GLP-1 agonist is an option. A sulfonylurea may be added to these interventions if necessary. Further adjustments should be made if A1C target is not achieved.

For more information, read the full ADA/EASD consensus statement for the medical management of hyperglycemia in type 2 diabetes.

Indication and Usage

BYETTA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

• Not a substitute for insulin and should not be used in patients with type 1 diabetes or diabetic ketoacidosis.
• Concurrent use with prandial insulin cannot be recommended.
• Has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using BYETTA; consider other antidiabetic therapies for these patients.

Important Safety Information for BYETTA^® (exenatide) injection

Contraindications

• BYETTA is contraindicated in patients with prior severe hypersensitivity reactions to exenatide or to any of the product components.

Warnings and Precautions

• Based on postmarketing data BYETTA has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. After initiation and dose increases of BYETTA, observe patients carefully for pancreatitis (persistent severe abdominal pain, sometimes radiating to the back, with or without vomiting). If pancreatitis is suspected, BYETTA should be discontinued promptly. BYETTA should not be restarted if pancreatitis is confirmed.
• Increased risk of hypoglycemia when used in combination with glucose-independent insulin secretagogues (eg, sulfonylureas); reduction of the sulfonylurea dose may be needed. When used with insulin, evaluate and consider reducing the insulin dose in patients at increased risk of hypoglycemia.
• Postmarketing reports of altered renal function, including increased serum creatinine, renal impairment, worsened chronic renal failure, and acute renal failure, sometimes requiring hemodialysis and kidney transplantation. BYETTA should not be used in patients with severe renal impairment or end-stage renal disease. Use with caution in patients with renal transplantation or when initiating or escalating the dose in patients with moderate renal failure.
• Not recommended in patients with severe gastrointestinal disease (eg, gastroparesis).
• Patients may develop antibodies to exenatide. In 3 registration trials, antibody levels were measured in 90% of patients, with up to 4% of patients having high-titer antibodies and attenuated glycemic response. If worsening of or failure to achieve adequate glycemic control occurs, consider alternative antidiabetic therapy.
• Postmarketing reports of serious hypersensitivity reactions (eg, anaphylaxis and angioedema). If this occurs, patients should discontinue BYETTA and other suspect medications and promptly seek medical advice.
• No clinical studies establishing conclusive evidence of macrovascular risk reduction with BYETTA or any other antidiabetic drug.

Adverse Reactions

• Most common adverse reactions in registration trials associated with BYETTA vs placebo (PBO): nausea (44% vs 18%), vomiting (13% vs 4%), and diarrhea (13% vs 6%). Other adverse reactions ≥5% and more than PBO: feeling jittery, dizziness, headache, and dyspepsia. With a thiazolidinedione (TZD), adverse reactions were similar; as monotherapy, most common was nausea (8% vs 0%). With insulin glargine: nausea (41% vs 8%), vomiting (18% vs 4%), diarrhea (18% vs 8%), headache (14% vs 4%), constipation (10% vs 2%), dyspepsia (7% vs 2%), asthenia (5% vs 1%).
• Hypoglycemia incidence, BYETTA vs PBO, with metformin (MET): 5.3% (10 mcg) and 4.5% (5 mcg) vs 5.3%; with SFU, 35.7% (10 mcg) and 14.4% (5 mcg) vs 3.3%; with MET + SFU, 27.8% (10 mcg) and 19.2% (5 mcg) vs 12.6%; with TZD, 10.7% (10 mcg) vs 7.1%; as monotherapy, 3.8% (10 mcg) and 5.2% (5 mcg) vs 1.3%; with insulin glargine, 24.8% (10 mcg) vs 29.5%.
• Withdrawals: as monotherapy, 2 of 155 BYETTA patients withdrew due to headache and nausea vs 0 PBO; with MET and/or SFU vs PBO, nausea (3% vs <1%) and vomiting (1% vs 0); with TZD ± MET, nausea (9%) and vomiting (5%), with <1% of PBO patients withdrawing due to nausea; with insulin glargine vs PBO, nausea (5.1% vs 0), vomiting (2.9% vs 0).

Drug Interactions

• BYETTA slows gastric emptying and can reduce the extent and rate of absorption of orally administered drugs. Use with caution with medications that have a narrow therapeutic index or require rapid gastrointestinal absorption. Medications dependent on threshold concentrations for efficacy should be taken at least 1 hour before BYETTA.
• Postmarketing reports of increased international normalized ratio (INR) sometimes associated with bleeding with concomitant use of warfarin. Monitor INR frequently until stable upon initiation or alteration of BYETTA.

Use in Specific Populations

• Based on animal data, BYETTA may cause fetal harm and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
• Caution should be exercised when administered to a nursing woman.
• Safety and effectiveness have not been established in pediatric patients.

For complete safety profile and other important prescribing considerations, see the Prescribing Information and Medication Guide.

Reference

1. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care. 2009;32(1):193-203.