Efficacy and Safety of Dulaglutide Monotherapy Versus Metformin in Type 2 Diabetes in a Randomized Controlled Trial (AWARD-3)

OBJECTIVE: Compare the efficacy and safety of monotherapy with dulaglutide, a once-weekly GLP-1 receptor agonist, to metformin-treated patients with type 2 diabetes. The primary objective compared dulaglutide 1.5 mg and metformin on change from baseline glycosylated hemoglobin A1c (HbA1c) at 26 weeks. RESEARCH DESIGN AND METHODS: This 52-week double-blind study randomized patients to subcutaneous dulaglutide 1.5 mg, dulaglutide 0.75 mg, or metformin. Patients (N = 807) had HbA1c ≥6.5% (≥48 mmol/mol) and ≤9.5% (≤80 mmol/mol) with diet and exercise alone or low-dose oral antihyperglycemic medication (OAM) monotherapy; OAMs were discontinued at beginning of lead-in period. RESULTS: At 26 weeks, changes from baseline HbA1c (least squares [LS] mean ± SE) were: dulaglutide 1.5 mg, -0.78 ± 0.06% (-8.5 ± 0.70 mmol/mol); dulaglutide 0.75 mg, -0.71 ± 0.06% (-7.8 ± 0.70 mmol/mol); and metformin, -0.56 ± 0.06% (-6.1 ± 0.70 mmol/mol). Dulaglutide 1.5 and 0.75 mg were superior to metformin (LS mean difference): -0.22% (-2.4 mmol/mol) and -0.15% (-1.6 mmol/mol) (one-sided P < 0.025, both comparisons), respectively. Greater percentages reached HbA1c targets <7.0% (<53 mmol/mol) and ≤6.5% (≤48 mmol/mol) with dulaglutide 1.5 and 0.75 mg compared with metformin (P < 0.05, all comparisons). No severe hypoglycemia was reported. Compared with metformin, decrease in weight was similar with dulaglutide 1.5 mg and smaller with dulaglutide 0.75 mg. Over 52 weeks, nausea, diarrhea, and vomiting were the most common adverse events; incidences were similar between dulaglutide and metformin. CONCLUSIONS: Dulaglutide improves glycemic control and is well tolerated as monotherapy in patients with early stage type 2 diabetes.