Placebo‐controlled, randomized trial of the addition of once‐weekly glucagon‐like peptide‐1 receptor agonist dulaglutide to titrated daily insulin glargine in patients with type 2 diabetes ( AWARD ‐9)

Aim To compare the addition of weekly dulaglutide vs the addition of placebo to titrated glargine in patients with type 2 diabetes ( T2D ) with sub‐optimum glycated haemoglobin ( HbA1c ) concentration. Materials and Methods Patients ( N  = 300) from this phase III , double‐blind, parallel‐arm, placebo‐controlled study were randomized to weekly subcutaneous injections of dulaglutide 1.5 mg or placebo with titrated daily glargine (mean ± standard deviation baseline dose: 39 ± 22 U), with or without metformin (≥1500 mg/d). The primary endpoint was superiority of dulaglutide/glargine to placebo/glargine with regard to change from baseline in HbA1c level at 28 weeks. Results Least squares ( LS ) mean ± standard error (s.e.) HbA1c changes from baseline were −1.44 ± 0.09% (−15.74 ± 0.98 mmol/mol) with dulaglutide/glargine and −0.67 ± 0.09% (−7.32 ± 0.98 mmol/mol) with placebo/glargine at 28 weeks ( LS mean difference [95% confidence interval] −0.77% [−0.97, −0.56]; P  < .001). Body weight decreased with dulaglutide/glargine and increased with placebo/glargine ( LS mean difference: −2.41 ± 0.39 kg; P  < .001). Increases from baseline in mean glargine dose were significantly smaller with dulaglutide/glargine vs placebo/glargine (13 ± 2 U [0.1 ± 0.02 U/kg] vs 26 ± 2 U [0.3 ± 0.02 U/kg], respectively; P  < .001; LS mean ± s.e. final dose: dulaglutide/glargine, 51 ± 2 U; placebo/glargine, 65 ± 2 U). The hypoglycaemia rate (≤3.9 mmol/L threshold) was 7.69 ± 15.15 and 8.56 ± 16.13 events/patient/year, respectively ( P  = .488). One episode of severe hypoglycaemia occurred in the dulaglutide/glargine group. Common gastrointestinal adverse events with dulaglutide were nausea (12.0%), diarrhoea (11.3%) and vomiting (6.0%). Conclusions Weekly dulaglutide 1.5 mg added to basal insulin is an efficacious and well tolerated treatment option for patients with T2D .