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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)

2017; Wiley; Volume: 19; Issue: 7 Linguagem: Inglês

10.1111/dom.12937

1463-1326

Paolo Pozzilli, Paul Norwood, Esteban Jódar, Melanie J. Davies, T. Iványi, Honghua Jiang, D. Bradley Woodward, Zvonko Miličević,

Pancreatic function and diabetes

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 .