For US Healthcare Professionals
Clinical Efficacy
BYETTA vs insulin lispro
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Study design
4B study: BYETTA BID vs insulin lispro TID
4B : Basal Insulin Glargine, Exenatide BID, and Metformin Therapy or Basal Insulin Glargine, Bolus Insulin Lispro, and Metformin Therapy
Objective: Compare the efficacy and safety of BYETTA (extenatide) injection, a shortacting GLP-1 receptor agonist, or bolus insulin lispro in patients inadequately controlled on a regimen of titrated insulin glargine plus metformin.
- Insulin glargine titration1,2: The INITIATE (INITiate Insulin by Aggressive Titration and Education) algorithm2 was utilized for IG titration during the BIO phase and following the initial IG reductions at randomization. At randomization, the daily IG dose in the BYETTA group was reduced up to 10% or more when A1C was ≤8%; in the IL group, the daily IG dose was reduced by one-half or one-third at the investigator’s discretion. In both groups, bedtime IG dose was titrated to an FPG of 100 mg/dL or lower without hypoglycemia (ie, glucose <54 mg/dL), based on self-monitored blood glucose and the use of a patient dosing aid.
Patients were instructed to take IG at bedtime and record daily date, time, and dose/units in a diary. Based on the average of 3 consecutive FPG values, doses of IG were increased when FPG exceeded 100 mg/dL. If fasting blood glucose was less than 72 mg/dL with symptomatic hypoglycemia, which occurred without reason, patients decreased the glargine dose. - Insulin lispro titration1: IL was titrated to a premeal glucose of 100 to 108 mg/dL based on self-monitored blood glucose and the use of a patient dosing aid. Patients were instructed to record date, dose, time of dose, and dose/units in a diary and test blood glucose immediately before injections and starting a meal. If premeal glucose was >108 mg/dL, IL doses were increased based on the dosing aid.
Mean baseline characteristics at randomization
- BYETTA arm: 52% male, 90% Caucasian; age, 60 years (mean); A1C, 8.3%; weight, 91.1 kg (200.4 lb); FPG, 7.1 mmol/L (127.8 mg/dL); metformin daily dose, 2038 mg; insulin glargine, 61.5 U/day; median duration of diabetes, 12 years.
- Insulin lispro arm: 51% male, 87% Caucasian; age, 59 years; A1C, 8.2%; weight, 89.4 kg (196.7 lb); FPG, 7.1 mmol/L (127.8 mg/dL); metformin daily dose, 1998 mg; insulin glargine, 61.1 U/day; median duration of diabetes, 11 years.
- Baseline insulin dosing: At the start of the BIO phase, the insulin glargine dose was 40.7 U/day in the enrolled population (N = 917), 34.5 U/day among the responders (N = 92 with A1C ≤7%), and 40.6 U/day among nonresponders (N = 652 with A1C >7%). At the end of the BIO phase, the insulin dose had been titrated to 56.8 U/day, 47.3 U/day, and 58.0 U/day in the enrolled, responder, and nonresponder population, respectively.
Select Important Safety Information: Warnings and Precautions
- Renal Impairment: 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. 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.
- Gastrointestinal Disease: Because exenatide is commonly associated with gastrointestinal adverse reactions, BYETTA is not recommended in patients with severe gastrointestinal disease (eg, gastroparesis).
- Immunogenicity: 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.
- Hypersensitivity: 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.
A1C reduction
In appropriate adult patients with type 2 diabetes uncontrolled on insulin glargine and metformin in addition to diet and exercise
BYETTA (exenatide) injection provided powerful A1C reductions similar to insulin lispro at 30 weeks
- Abbreviations: BL, baseline; LS, least squares; PP, per-protocol population; SE, standard error.
- Primary endpoint was change in A1C from randomization to 30 weeks with a noninferiority margin of 0.4% in the PP population.
BYETTA 5 mcg BID for 1 month, followed by BYETTA 10 mcg BID for the remainder of the 30-week study.
- BYETTA® (exenatide) injection met the primary endpoint of noninferiority to insulin lispo1
- BYETTA BID reduced A1C by -1.13% vs -1.10% for insulin lispro TID1
Additional benefit of weight loss*
- Abbreviations: BL, baseline; Ls, least squares; PP, per-protocol population; SE, standard error.
- At 30 weeks, BYETTA treatment resulted in a 5.5-lb reduction of body weight compared to insulin lispro, which increased body weight by 4.6 lb1
BYETTA is not indicated for weight loss.
*Weight reduction was a secondary end point
Select Important Safety Information: Warnings and Precautions
- Hypoglycemia: Increased risk of hypoglycemia when used in combination with a sulfonylurea (SU) or when used with a glucose-independent insulin secretagogues (eg, meglitinides). Clinicians may consider reducing the SU dose in patients receiving BYETTA to reduce the risk of hypoglycemia. When used with insulin, evaluate and consider reducing the insulin dose in patients at increased risk of hypoglycemia.
- Renal Impairment: 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. 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.
- Gastrointestinal Disease: Because exenatide is commonly associated with gastrointestinal adverse reactions, BYETTA is not recommended in patients with severe gastrointestinal disease (eg, gastroparesis).
Clinical summary
- Significantly greater A1C reduction of 1.7% compared to 1.0% for titrated insulin glargine alone.*
- Helped 57% of patients get to an A1C < 7% compared to 30% of patients on insulin glargine alone, and provided the potential for weight loss.†
- Rate of hypoglycemia for BYETTA plus titrated insulin glargine vs placebo plus titrated insulin glargine was 24.8% vs 29.5%, respectively.‡
- Nausea, the most common adverse event, was 41% for BYETTA vs 8% for placebo.
BYETTA provided powerful A1C reductions similar to mealtime insulin with the additional benefit of weight loss1*
In a head-to-head study vs mealtime insulin, BYETTA demonstrated:
- Powerful A1C reductions similar to insulin lispro at 30 weeks (-1.13% vs -1.10%, respectively†)
- The additional benefit of weight loss* vs insulin lispro, with a 10-lb difference between groups
- Lower incidences of minor hypoglycemia (BYETTA, 30%; insulin lispro, 41%) and major hypoglycemia (BYETTA, 0.6%; insulin lispro, 2.2%)
BYETTA is not indicated for weight loss.
*Weight reduction was a secondary end point
-
†
- Baseline: BYETTA, 8.3%; insulin lispro,
- 8.2%.
- Reference: 1. Diamant M, Nauck MA, Shaginian R, et al; for the BYETTA vs mealtime insulin Study Group. Glucagon-like peptide-1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014;37(10):2763-2773.
This product information is intended for US Healthcare Professionals only.
BYETTA, the BYETTA logo, and BYETTA By Your Side are registered trademarks of the AstraZeneca group of companies. The Double B logo is a trademark of the AstraZeneca group of companies. All other trademarks are property of their respective owners.
© 2015 AstraZeneca. All rights reserved. 1817006-3025920 Last Updated 01/15
Indication and Important Limitations of Use for BYETTA
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 has not been studied and cannot be recommended.
- BYETTA has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, based on postmarketing data. 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.
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Adults with type 2 diabetes on insulin glargine alone or in combination with metformin and/or a TZD were enrolled in a 30-week, randomized, double-blind, placebo-controlled clinical study to receive either BYETTA (n=137) or placebo (n=122) in addition to titrated insulin glargine. In both arms, under investigator guidance, insulin was titrated to achieve a targeted fasting glucose level of <100 mg/dL using the Treat-to-Target algorithm. Upon adding BYETTA to insulin glargine, patients with an A1C ≤8% were instructed to decrease their insulin glargine dose by 20%; patients with an A1C >8% maintained their current insulin dose. Patients receiving BYETTA were titrated from the 5-mcg dose to the 10-mcg dose after the first 4 weeks.1 Please see full Prescribing Information for full dosing algorithm.
- 30-week trial of BYETTA added to insulin glargine ± MET and/or TZD vs PBO: 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%).
- The most frequently reported adverse reactions leading to withdrawal for Byetta-treated patients were nausea (5.1%) and vomiting (2.9%). No placebo-treated patients withdrew due to nausea or vomiting.