Journal Article

Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial

Forst, Thomas, Povedano, Santiago Tofé, Atisso, Charles, González, José G González, Dungan, Kathleen M, Fahrbach, Jessie L, Sealls, Whitney

2014

Overview

Dulaglutide and liraglutide, both glucagon-like peptide-1 (GLP-1) receptor agonists, improve glycaemic control and reduce weight in patients with type 2 diabetes. In a head-to-head trial, we compared the safety and efficacy of once-weekly dulaglutide with that of once-daily liraglutide in metformin-treated patients with uncontrolled type 2 diabetes. We did a phase 3, randomised, open-label, parallel-group study at 62 sites in nine countries between June 20, 2012, and Nov 25, 2013. Patients with inadequately controlled type 2 diabetes receiving metformin (≥1500 mg/day), aged 18 years or older, with glycated haemoglobin (HbA1c) 7·0% or greater (≥53 mmol/mol) and 10·0% or lower (≤86 mmol/mol), and body-mass index 45 kg/m2 or lower were randomly assigned to receive once-weekly dulaglutide (1·5 mg) or once-daily liraglutide (1·8 mg). Randomisation was done according to a computer-generated random sequence with an interactive voice response system. Participants and investigators were not masked to treatment allocation. The primary outcome was non-inferiority (margin 0·4%) of dulaglutide compared with liraglutide for change in HbA1c (least-squares mean change from baseline) at 26 weeks. Safety data were collected for a further 4 weeks' follow-up. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01624259. We randomly assigned 599 patients to receive once-weekly dulaglutide (299 patients) or once-daily liraglutide (300 patients). 269 participants in each group completed treatment at week 26. Least-squares mean reduction in HbA1c was −1·42% (SE 0·05) in the dulaglutide group and −1·36% (0·05) in the liraglutide group. Mean treatment difference in HbA1c was −0·06% (95% CI −0·19 to 0·07, pnon-inferiority<0·0001) between the two groups. The most common gastrointestinal adverse events were nausea (61 [20%] in dulaglutide group vs 54 [18%] in liraglutide group), diarrhoea (36 [12%] vs 36 [12%]), dyspepsia (24 [8%] vs 18 [6%]), and vomiting (21 [7%] vs 25 [8%]), with similar rates of study or study drug discontinuation because of adverse events between the two groups (18 [6%] in each group). The hypoglycaemia rate was 0·34 (SE 1·44) and 0·52 (3·01) events per patient per year, respectively, and no severe hypoglycaemia was reported. Once-weekly dulaglutide is non-inferior to once-daily liraglutide for least-squares mean reduction in HbA1c, with a similar safety and tolerability profile. Eli Lilly and Company.

• Publisher: Elsevier Ltd,Elsevier,Elsevier Limited
• Subject: Analysis of Variance / Biological and medical sciences / Blood Glucose - metabolism / Blood pressure / Clinical trials / Diabetes / Diabetes Mellitus, Type 2 - blood / Diabetes Mellitus, Type 2 - drug therapy / Diabetes. Impaired glucose tolerance / Drug Administration Schedule / Drug dosages / Drug therapy / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Enzymes / Etiopathogenesis. Screening. Investigations. Target tissue resistance / Fasting - blood / Female / General aspects / Glucagon-Like Peptide 1 - administration & dosage / Glucagon-Like Peptide 1 - adverse effects / Glucagon-Like Peptide 1 - analogs & derivatives / Glucagon-Like Peptides - administration & dosage / Glucagon-Like Peptides - adverse effects / Glucagon-Like Peptides - analogs & derivatives / Glycated Hemoglobin A - metabolism / Humans / Hypoglycemic Agents - administration & dosage / Hypoglycemic Agents - adverse effects / Immunoglobulin Fc Fragments - administration & dosage / Immunoglobulin Fc Fragments - adverse effects / Internal Medicine / Liraglutide / Male / Medical sciences / Metformin - therapeutic use / Middle Aged / Recombinant Fusion Proteins - administration & dosage / Recombinant Fusion Proteins - adverse effects / Safety / Treatment Outcome