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)

Abstract

OBJECTIVE To compare efficacy and safety of dulaglutide at doses of 3.0 and 4.5 mg versus 1.5 mg in patients with type 2 diabetes inadequately controlled with metformin. RESEARCH DESIGN AND METHODS Patients were randomly assigned to once-weekly dulaglutide 1.5 mg, 3.0 mg, or 4.5 mg for 52 weeks. The primary objective was determining 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 (regardless of treatment discontinuation or rescue medication) and efficacy (on treatment without rescue medication) in all randomly assigned patients. RESULTS Mean baseline HbA1c and BMI in randomly assigned patients (N 5 1,842) was 8.6% (70 mmol/mol) and 34.2 kg/m2, respectively. At 36 weeks, dulaglutide 4.5 mg provided superior HbA1c reductions compared with 1.5 mg (treatment-regimen estimand: 21.77 vs. 21.54% [219.4 vs. 216.8 mmol/mol], estimated treatment difference [ETD] 20.24% (22.6 mmol/mol), P < 0.001; efficacy estimand: 21.87 vs. 21.53% [220.4 vs. 216.7 mmol/mol], ETD 20.34% (23.7 mmol/mol), P < 0.001). Dulaglutide 3.0 mg was superior to 1.5 mg for reducing HbA1c, using the efficacy estimand (ETD 20.17% [21.9 mmol/mol]; P 5 0.003) but not the treatment-regimen estimand (ETD 20.10% [21.1 mmol/mol]; P 5 0.096). Dulaglutide 4.5 mg was superior to 1.5 mg for weight loss at 36 weeks for both estimands (treatment regimen: 24.6 vs. 23.0 kg, ETD 21.6 kg, P < 0.001; efficacy: 24.7 vs. 23.1 kg, ETD 21.6 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%). CONCLUSIONS In patients with type 2 diabetes inadequately controlled by metformin, escalation from dulaglutide 1.5 mg to 3.0 mg or 4.5 mg provided clinically relevant, doserelated reductions in HbA1c and body weight with a similar safety profile.