A 24-week study to evaluate the efficacy and safety of once-weekly dulaglutide added on to glimepiride in type 2 diabetes (AWARD-8)

Abstract

Aims: To evaluate the safety and efficacy of once-weekly dulaglutide 1.5mg, a long-acting glucagon-like peptide-1 receptor agonist, compared with placebo in patients with type 2 diabetes (T2D) on glimepiride monotherapy. Methods: This phase III, randomized (4:1; dulaglutide:placebo), double-blind, placebo-controlled, 24-week study compared the safety and efficacy of once-weekly dulaglutide 1.5mg with placebo in sulphonylurea-treated (≥half-maximal dose, stable ≥3months) patients (N=300) with T2D and inadequate glycaemic control [glycated haemoglobin (HbA1c) ≥7.5 and ≤9.5% (≥58 mmol/mol and ≤80 mmol/mol)]. Analysis was carried out according to intention-to-treat. Results: At baseline, the mean participant age was 58years; mean HbA1c was 8.4% (68mmol/mol) and mean weight was 85.5kg. Dulaglutide 1.5mg was superior to placebo at 24weeks for HbA1c reduction from baseline with a between-group HbA1c difference of -1.3% [95% confidence interval (CI) -1.6, -1.0] or -14mmol/mol (95% CI -17, -11); p<0.001. A greater proportion of participants in the dulaglutide group reached an HbA1c level of <7.0% (53mmol/mol) compared with placebo (55.3% vs 18.9%; p<0.001). Dulaglutide significantly decreased fasting serum glucose from baseline compared with placebo (between-group difference -1.86mmol/l (95% CI -2.58, -1.14) or -33.54mg/dl (95% CI -46.55, -20.53); p<0.001. Weight was decreased significantly from baseline in the dulaglutide group (p<0.001); the between-group difference was not significant. The most common treatment-emergent adverse events for dulaglutide 1.5mg were gastrointestinal: nausea (10.5%), diarrhoea (8.4%) and eructation (5.9%). Total hypoglycaemia was higher with dulaglutide 1.5mg vs placebo (2.37 and 0.07 events/participant/year, respectively; p=0.025). No severe hypoglycaemia was reported. Conclusions: Once-weekly dulaglutide 1.5mg had a favourable benefit/risk profile when added to glimepiride monotherapy.