Three 30-week, double-blind, placebo-controlled trials were conducted to evaluate the safety and efficacy of BYETTA in patients with type 2 diabetes whose glycemic control was inadequate with metformin alone, a sulfonylurea alone, or metformin in combination with a sulfonylurea. In addition, a 16-week, placebo-controlled trial was conducted where BYETTA was added to existing thiazolidinedione (pioglitazone or rosiglitazone) treatment, with or without metformin, in patients with type 2 diabetes with inadequate glycemic control.

In the 30-week trials, after a 4-week placebo lead-in period, patients were randomly assigned to receive BYETTA 5 mcg BID, BYETTA 10 mcg BID, or placebo BID before the morning and evening meals, in addition to their existing oral antidiabetic agent. All patients assigned to BYETTA initially received 5 mcg BID for 4 weeks. After 4 weeks, those patients either continued to receive BYETTA 5 mcg BID or had their dose increased to 10 mcg BID. Patients assigned to placebo received placebo BID throughout the study. A total of 1446 patients were randomized in the three 30-week trials: 991 (69%) were Caucasian, 224 (16%) were Hispanic, and 174 (12%) were Black. Mean HbA1c values at baseline for the trials ranged from 8.2% to 8.7%.

In the placebo-controlled trial of 16 weeks duration, BYETTA (n = 121) or placebo (n = 112) was added to existing thiazolidinedione (pioglitazone or rosiglitazone) treatment, with or without metformin. Randomization to BYETTA or placebo was stratified based on whether the patients were receiving metformin. BYETTA treatment was initiated at a dose of 5 mcg BID for 4 weeks then increased to 10 mcg BID for 12 more weeks. Patients assigned to placebo received placebo BID throughout the study. BYETTA or placebo was injected subcutaneously before the morning and evening meals. In this trial, 79% of patients were taking a thiazolidinedione and metformin and 21% were taking a thiazolidinedione alone. The majority of patients (84%) were Caucasian, 8% were Hispanic and 3% were Black. The mean baseline HbA1c values were 7.9% for BYETTA and placebo.

The primary endpoint in each study was the mean change in HbA1c from baseline to study end (or early discontinuation). Table 7 summarizes the study results for the 30-week and 16-week clinical trials.

HbA1c

The addition of BYETTA to a regimen of metformin, a sulfonylurea, or both, resulted in statistically significant reductions from baseline in HbA1c compared with patients receiving placebo added to these agents in the three controlled trials (Table 7).

In the 16-week trial of BYETTA add-on to thiazolidinediones, with or without metformin, BYETTA resulted in statistically significant reductions from baseline in HbA1c compared with patients receiving placebo (Table 7).

Postprandial Glucose

Postprandial glucose was measured after a mixed meal tolerance test in 9.5% of patients participating in the 30-week add-on to metformin, add-on to sulfonylurea, and add-on to metformin in combination with sulfonylurea clinical trials. In this pooled subset of patients, BYETTA reduced postprandial plasma glucose concentrations in a dose-dependent manner. The mean (SD) change in 2-h postprandial glucose concentration following administration of BYETTA at Week 30 relative to baseline was -63 (65) mg/dL for 5 mcg BID (n = 42), -71 (73) mg/dL for 10 mcg BID (n = 52), and +11 (69) mg/dL for placebo BID (n = 44).