Efficacy and safety of once-weekly dulaglutide versus insulin glargine, both with prandial insulin lispro (+/- metformin), in an AWARD-4 subpopulation of patients with type 2 diabetes (T2D) and baseline HbA1c (≥7.5% and ≤11%) above the German recommended HbA1c treatment target range

Objective: German national treatment guidelines recommend HbA1c target range 6.5 – 7.5% for 'healthy' patients with T2D. Data from an open-label AWARD-4 subpopulation with baseline HbA1c ≥7.5% (above recommended target range) and ≤11% (˜80% intent-to-treat population) were analysed comparing dulaglutide vs. glargine, both with lispro ± metformin.

Methods: Efficacy and safety data from eligible patients uncontrolled on conventional insulin regimens receiving once-weekly dulaglutide 1.5 mg (N = 228) or glargine (N = 239) were compared post-hoc at 26 weeks (primary endpoint).

Results: In this subpopulation, (all least squares mean) HbA1c reduction for dulaglutide vs. glargine was 1.78% vs. 1.60% [difference (95% confidence interval): -0.18 (-0.36, +0.00)%] and weight change was -0.64 kg vs. +2.31 kg [difference (95% confidence interval): -2.95 (-3.66, -2.25)kg]. Proportions of dulaglutide- vs. glargine-treated patients achieving other endpoints were: HbA1c < 7%, 62.4% vs. 54.8% (p = 0.109); HbA1c < 7% without nocturnal or severe hypoglycaemia, 48.6% vs. 27.2% (p < 0.001); HbA1c < 7% without nocturnal or severe hypoglycaemia and weight gain, 27.1% vs. 5.7% (p < 0.001). Proportions of dulaglutide- vs. glargine-treated patients with ≥1 documented symptomatic or nocturnal hypoglycaemia (≤70 mg/dl) were, respectively, 77.3% vs. 82.9% (p = 0.137) and 47.1% vs. 60.7% (p = 0.003). Severe hypoglycaemia affected five (2.2%) vs. ten (4.2%) patients (p = 0.297). Adverse events (AEs) and serious AEs occurred in 68.4% vs. 61.1% (p = 0.097) and 4.8% vs. 12.1% (p = 0.005) of patients. Gastrointestinal AEs were more common with dulaglutide than glargine (p < 0.001).

Conclusions: This subpopulation with baseline HbA1c above recommended target range achieved significant HbA1c reduction with either treatment, although a larger proportion of patients reached combined treatment goals with dulaglutide 1.5 mg vs. glargine.