Efficacy of investigational dulaglutide doses overall and by baseline HbA1c and Body Mass Index (BMI): exploratory subgroup analyses of the AWARD-11 trial

Background and aims The AWARD-11 trial assessed whether escalation of dulaglutide from 1.5 mg to 3 mg and 4.5 mg further improves glucose and body weight (BW) with an acceptable safety profile in patients with T2 D inadequately controlled with metformin monotherapy. Exploratory prespecified subgroup analyses assessed the effect on HbA1c and BW reduction by baseline HbA1c (< 8.5 % or ≥8.5 %) and BMI (< or ≥ median [33.2 kg/m2]). Materials and methods: 1,842 patients were randomised (1:1:1) to once-weekly dulaglutide 1.5 mg (n=612), 3 mg (n=616), and 4.5 mg (n=614). The primary outcome was HbA1c change from baseline at 36 weeks. Secondary outcomes included percentage of patients achieving HbA1c< 7 % at 36 weeks. Results: At baseline patients had a mean age of 57.1 years, HbA1c was 8.6 %, and BW was 95.7 kg. At 36-weeks, dulaglutide 3 mg and 4.5 mg were superior to 1.5 mg for HbA1c change (1.5 mg, -1.5%; 3 mg, -1.7 % [p=0.003]; 4.5 mg, -1.9%[p< 0.001]), percentage of patients achieving HbA1c< 7 % (1.5 mg, 57%; 3.0 mg, 65 % [p=0.006]; 4.5 mg, 71%[p< 0.001]) and BW (1.5 mg, -3.1kg; 3 mg, -4.0 kg [p=0.001]; 4.5 mg, -4.7kg[p< 0.001]). HbA1c improvements and BW reduction were dose-related in each HbA1c and BMI subgroup. HbA1c improvement was larger in the higher baseline HbA1c subgroup. BW reduction was larger among patients with lower baseline HbA1c and greater in higher baseline BMI subgroup. Conclusions: In patients with T2 D and inadequate glycaemic control on metformin, escalation from dulaglutide 1.5 mg to 3 mg or 4.5 mg provided clinically relevant, dose-related improvements in HbA1c and BW overall and in subgroups of baseline HbA1c and BMI.

Publication History

Article published online:
06 May 2021