Abstract
INTRODUCTION: This exploratory post hoc analysis investigated the relative changes in glycated haemoglobin (HbA(1c)) in patients with type 2 diabetes mellitus (T2DM) treated with dulaglutide versus active comparators across a continuous range of baseline HbA(1c) values using data from three phase III randomised controlled trials. METHODS: Data from patients receiving once-weekly dulaglutide 0.75 and 1.5 mg, once-daily sitagliptin 100 mg, once-daily liraglutide 1.8 mg or twice-daily exenatide 10 μg in the intent-to-treat populations in the AWARD-5, AWARD-6 and AWARD-1 trials were analysed using last observation carried forward analysis of covariance. Starting with the predefined statistical model from each study, the type of association between HbA(1c) baseline and change at 26 weeks was modelled. Consistency of treatment effect was assessed via treatment-by-baseline HbA(1c) interaction terms. RESULTS: Improvements in HbA(1c) occurred in all treatment groups across the entire baseline HbA(1c) range. The relationship between HbA(1c) baseline and magnitude of change was linear in all treatment groups, with greater reductions in patients with higher baseline HbA(1c) values. Across the continuum of baseline HbA(1c) values, patients treated with dulaglutide 1.5 mg achieved a similar mean HbA(1c) reduction to patients receiving liraglutide 1.8 mg and a greater reduction than patients receiving twice-daily exenatide or sitagliptin. In AWARD-5, the treatment-by-baseline HbA(1c) interaction P value (0.001) demonstrated progressively greater HbA(1c) reduction in dulaglutide-treated compared with sitagliptin-treated patients as baseline HbA(1c) increased. CONCLUSION: Our results suggest that dulaglutide is an appropriate therapeutic option for patients with T2DM across a wide range of baseline HbA(1c) values, including those with poor metabolic control. FUNDING: Eli Lilly and Company. Plain language summary available for this article.