Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus Dulaglutide 1.5 mg in Metformin-Treated Patients With Type 2 Diabetes in a Randomized Controlled Trial (AWARD-11)
Research Design and Methods: Patients were randomized to once weekly dulaglutide 1.5 mg, 3.0 mg, or 4.5 mg for 52 weeks. Primary objective was superiority of dulaglutide 3.0 mg and/or 4.5 mg over 1.5 mg in HbA1c reduction at 36 weeks. Secondary superiority objectives included change in body weight. Two estimands addressed efficacy objectives: treatment-regimen estimand (regardless of treatment discontinuation or rescue medication) and efficacy estimand (on treatment without rescue medication) in all randomized patients.
Results: Mean baseline HbA1c and BMI in randomized patients (N=1842) was 8.6% (70 mmol/mol) and 34.2 kg/m2, respectively. At 36 weeks, dulaglutide 4.5 mg provided superior HbA1c reductions compared to 1.5 mg (treatment-regimen estimand: -1.77 vs ‑1.54% [-19.4 vs -16.8 mmol/mol], estimated treatment difference [ETD] -0.24% (-2.6 mmol/mol); P<0.001; efficacy estimand: -1.87 vs ‑1.53% [‑20.4 vs -16.7 mmol/mol], ETD -0.34% (-3.7 mmol/mol); P<0.001). Dulaglutide 3.0 mg was superior to 1.5 mg on HbA1c reduction using the efficacy estimand (ETD -0.17% [-1.9 mmol/mol]; P=0.003) but not the treatment-regimen estimand (ETD -0.10% [-1.1 mmol/mol ]; P=0.096). Dulaglutide 4.5 mg was superior to 1.5 mg for weight loss at 36 weeks for both estimands (treatment-regimen estimand: -4.6 vs -3.0 kg, ETD -1.6 kg; P<0.001; efficacy estimand: -4.7 vs -3.1 kg; ETD -1.6 kg; P<0.001). Common adverse events through 36 weeks included nausea (1.5 mg, 13.4%; 3 mg, 15.6%; 4.5 mg, 16.4%) and vomiting (1.5 mg, 5.6%; 3 mg, 8.3%; 4.5 mg, 9.3%).
Conclusion: In patients with type 2 diabetes inadequately controlled on metformin, escalation from dulaglutide 1.5 mg to 3.0 mg or 4.5 mg provided clinically relevant, dose-related reductions in HbA1c and body weight with a similar safety profile.
