Efficacy and Safety of Once-Weekly Dulaglutide Versus Insulin Glargine in Patients With Type 2 Diabetes on Metformin and Glimepiride (AWARD-2)

OBJECTIVEThis study compared the efficacy and safety of once-weekly dulaglutide, a glucagon-like peptide-1 receptor agonist, with daily insulin glargine, both combined with maximally tolerated doses of metformin and glimepiride in patients with type 2 diabetes. The primary objective was noninferiority of dulaglutide 1.5 mg to glargine in the HbA(1c) change from baseline at 52 weeks.RESEARCH DESIGN AND METHODSIn this 78-week, open-label study, 810 patients were randomized to dulaglutide 1.5 mg, dulaglutide 0.75 mg, or glargine.RESULTSThe baseline mean SD HbA(1c) was 8.1 +/- 1.0% (65.5 +/- 10.8 mmol/mol). The least squares mean +/- SE HbA(1c) change from baseline to the primary end point was -1.08 +/- 0.06% (-11.8 +/- 0.7 mmol/mol) for dulaglutide 1.5 mg, -0.76 +/- 0.06% (-8.3 +/- 0.7 mmol/mol) for dulaglutide 0.75 mg, and -0.63 +/- 0.06% (-6.9 +/- 0.7 mmol/mol) for glargine, with an end point mean +/- SD dose of 29 +/- 26 units (0.33 +/- 0.24 units/kg), and a fasting plasma glucose (mean +/- SD) of 118 +/- 23 mg/dL from self-monitored plasma glucose. Statistical criteria for superiority were met with dulaglutide 1.5 mg and for noninferiority with dulaglutide 0.75 mg. More patients on dulaglutide 1.5 mg achieved HbA(1c) targets <7.0% (53 mmol/mol) versus glargine (P < 0.001). Body weight decreased with dulaglutide and increased with glargine. Total hypoglycemia rates were lower with dulaglutide; severe hypoglycemia was minimal. Increases in pancreatic enzymes were observed for dulaglutide. Incidence of nausea (15.4, 7.7, and 1.5%) and diarrhea (10.6, 9.2, and 5.7%) were more common with dulaglutide 1.5 mg and 0.75 mg than with glargine.CONCLUSIONSOnce-weekly dulaglutide 1.5 mg, compared with daily insulin glargine without forced titration, demonstrated greater HbA(1c) reduction and weight loss, with a higher incidence of gastrointestinal adverse events and a lower risk of hypoglycemia.