Consistency of treatment effect across the range of baseline HbA1c in patients with type 2 diabetes mellitus (T2DM) treated with once-weekly dulaglutide or comparators in AWARD-1, -5 and -6

Objective: To characterise the relative effects of once-weekly dulaglutide (DU) and active comparators on change in HbA1c across the continuous range of baseline HbA1c values.

Methods: This exploratory post-hoc analysis included adult patients with T2DM randomised to DU1.5 mg, DU0.75 mg or exenatide 10mcg twice daily (AWARD-1; N = 835), DU1.5 mg, DU0.75 mg or sitagliptin 100 mg once daily (AWARD-5; N = 921), or DU1.5 mg or liraglutide 1.8 mg once daily (AWARD-6; N = 599), all with metformin (AWARD-5, -6) or metformin+pioglitazone (AWARD-1); placebo populations not included. Changes in HbA1c were evaluated at primary endpoint (AWARD-1, -6: 26 weeks; AWARD-5: 52 weeks) and analysed by study using LOCF ANCOVA with treatment-by-baseline HbA1c interaction terms.

Results: In all studies, all treatments reduced HbA1c from baseline across the entire baseline HbA1c range. DU1.5 mg showed greater (exenatide, sitagliptin) or similar (liraglutide) mean reductions in HbA1c versus the comparator across the entire baseline HbA1c range. In AWARD-1 and -6, there was no indication of a differential treatment effect of baseline HbA1c (p = 0.443 and p = 0.605, respectively). In AWARD-5, a differential treatment effect of baseline HbA1c was observed (p < 0.001), driven by the sitagliptin group, with more pronounced between-treatment differences in favour of DU as baseline HbA1c increased. Results were generally similar with DU0.75 mg in AWARD-1 and -5.

Conclusions: In these studies, improvements in HbA1c occurred with all treatments irrespective of baseline HbA1c. The relative effects on HbA1c of DU1.5 mg compared with active comparators were either consistent across the range of baseline HbA1c (exenatide, liraglutide) or the difference between treatments increased as baseline HbA1c increased (sitagliptin).