Efficacy and Safety of Dulaglutide Versus Sitagliptin After 52 Weeks in Type 2 Diabetes in a Randomized Controlled Trial (AWARD-5)

OBJECTIVE To compare the efficacy and safety of two doses of once-weekly dulaglutide, a glucagon-like peptide 1 receptor agonist, to sitagliptin in uncontrolled, metformin-treated patients with type 2 diabetes. The primary objective was to compare (for noninferiority and then superiority) dulaglutide 1.5 mg versus sitagliptin in change from baseline in glycosylated hemoglobin A(1c) (HbA(1c)) at 52 weeks. RESEARCH DESIGN AND METHODS This multicenter, adaptive, double-blind, parallel-arm study randomized patients (N = 1,098; mean baseline age 54 years; HbA(1c) 8.1% [65 mmol/mol]; weight 86.4 kg; diabetes duration 7 years) to dulaglutide 1.5 mg, dulaglutide 0.75 mg, sitagliptin 100 mg, or placebo (placebo-controlled period up to 26 weeks). The treatment period lasted 104 weeks, with 52-week primary end point data presented. RESULTS The mean HbA(1c) changes to 52 weeks were (least squares mean +/- SE): -1.10 +/- 0.06% (-12.0 +/- 0.7 mmol/mol), -0.87 +/- 0.06% (9.5 +/- 0.7 mmol/mol), and -0.39 +/- 0.06% (4.3 +/- 0.7 mmol/mol) for dulaglutide 1.5 mg, dulaglutide 0.75 mg, and sitagliptin, respectively. Both dulaglutide doses were superior to sitagliptin (P < 0.001, both comparisons). No events of severe hypoglycemia were reported. Mean weight changes to 52 weeks were greater with dulaglutide 1.5 mg (-3.03 +/- 0.22 kg) and dulaglutide 0.75 mg (-2.60 +/- 0.23 kg) compared with sitagliptin (-1.53 +/- 0.22 kg) (P < 0.001, both comparisons). The most common gastrointestinal treatment-emergent adverse events in dulaglutide 1.5- and 0.75-mg arms were nausea, diarrhea, and vomiting. CONCLUSIONS Both dulaglutide doses demonstrated superior glycemic control versus sitagliptin at 52 weeks with an acceptable tolerability and safety profile.