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)

Paolo Pozzilli, Paul Norwood, Esteban Jódar, Melanie J. Davies, Tibor Ivanyi, Honghua Jiang, D. Bradley Woodward, Zvonko Milicevic

Compare the addition of weekly dulaglutide versus the addition of placebo to titrated glargine in patients with type 2 diabetes (T2D) with sub-optimal HbA1c . Patients (N = 300) from this Phase 3, double-blind, parallel-arm, placebo-controlled study were randomised to weekly subcutaneous injections of dulaglutide 1.5 mg or placebo with titrated daily glargine (mean ± SD baseline dose: 39 ± 22 U), with or without metformin (≥1,500 mg/day). The primary objective was superiority of dulaglutide/glargine to placebo/glargine on change from baseline in HbA1c at 28 weeks. LSM ± SE 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 (LSM difference [95% CI]: -0.77% [-0.97%, -0.56%]; p < 0.001). Body weight reduced with dulaglutide/glargine and increased with placebo/glargine (LSM difference: -2.41 ± 0.39 kg; p < 0.001). Increases from baseline in mean glargine dose were significantly smaller with dulaglutide/glargine versus placebo/glargine (13 ± 2 U [0.1 ± 0.02 U/kg] versus 26 ± 2 U [0.3 ± 0.02 U/kg], respectively; p < 0.001; LSM ± SE final dose: dulaglutide/glargine, 51 ± 2 U; placebo/glargine, 65 ± 2 U). Hypoglycaemia rate (for ≤3.9 mmol/L threshold) was 7.69 ± 15.15 and 8.56 ± 16.13 events/patient/year, respectively (p = 0.488). One episode of severe hypoglycaemia occurred with dulaglutide/glargine. Common gastrointestinal adverse events with dulaglutide were nausea (12.0%), diarrhoea (11.3%), and vomiting (6.0%). Weekly dulaglutide 1.5 mg added to basal insulin is an efficacious and well tolerated treatment option for patients with T2D.