Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1).

OBJECTIVE: To compare the efficacy and safety of dulaglutide, a once-weekly GLP-1 receptor agonist, with placebo and exenatide in type 2 diabetic patients. The primary objective was to determine superiority of dulaglutide 1.5 mg versus placebo in HbA1c change at 26 weeks. RESEARCH DESIGN AND METHODS: This 52-week, multicenter, parallel-arm study (primary end point: 26 weeks) randomized patients (2:2:2:1) to dulaglutide 1.5 mg, dulaglutide 0.75 mg, exenatide 10 μg, or placebo (placebo-controlled period: 26 weeks). Patients were treated with metformin (1,500-3,000 mg) and pioglitazone (30-45 mg). Mean baseline HbA1c was 8.1% (65 mmol/mol). RESULTS: Least squares mean ± SE HbA1c change from baseline to the primary end point was -1.51 ± 0.06% (-16.5 ± 0.7 mmol/mol) for dulaglutide 1.5 mg, -1.30 ± 0.06% (-14.2 ± 0.7 mmol/mol) for dulaglutide 0.75 mg, -0.99 ± 0.06% (-10.8 ± 0.7 mmol/mol) for exenatide, and -0.46 ± 0.08% (-5.0 ± 0.9 mmol/mol) for placebo. Both dulaglutide doses were superior to placebo at 26 weeks (both adjusted one-sided P < 0.001) and exenatide at 26 and 52 weeks (both adjusted one-sided P < 0.001). Greater percentages of patients reached HbA1c targets with dulaglutide 1.5 mg and 0.75 mg than with placebo and exenatide (all P < 0.001). At 26 and 52 weeks, total hypoglycemia incidence was lower in patients receiving dulaglutide 1.5 mg than in those receiving exenatide; no dulaglutide-treated patients reported severe hypoglycemia. The most common gastrointestinal adverse events for dulaglutide were nausea, vomiting, and diarrhea. Events were mostly mild to moderate and transient. CONCLUSIONS: Both once-weekly dulaglutide doses demonstrated superior glycemic control versus placebo and exenatide with an acceptable tolerability and safety profile.