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 - PubMed (original) (raw)
Clinical Trial
. 2014 Oct 11;384(9951):1349-57.
doi: 10.1016/S0140-6736(14)60976-4. Epub 2014 Jul 10.
Affiliations
- PMID: 25018121
- DOI: 10.1016/S0140-6736(14)60976-4
Clinical Trial
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
Kathleen M Dungan et al. Lancet. 2014.
Erratum in
- Lancet. 2014 Oct 11:384(9951):1348
Abstract
Background: 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.
Methods: 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/m(2) 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.
Findings: 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.
Interpretation: Once-weekly dulaglutide is non-inferior to once-daily liraglutide for least-squares mean reduction in HbA1c, with a similar safety and tolerability profile.
Funding: Eli Lilly and Company.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Comment in
- Which incretin-based therapy for type 2 diabetes?
Scheen AJ. Scheen AJ. Lancet. 2014 Oct 11;384(9951):1325-7. doi: 10.1016/S0140-6736(14)61097-7. Epub 2014 Jul 10. Lancet. 2014. PMID: 25018117 No abstract available. - ACP Journal Club: in metformin-treated type 2 diabetes mellitus, weekly dulaglutide was noninferior to daily liraglutide for HbA1c levels.
Morey-Vargas OL, Shah P. Morey-Vargas OL, et al. Ann Intern Med. 2014 Nov 18;161(10):JC9. doi: 10.7326/0003-4819-161-10-201411180-02009. Ann Intern Med. 2014. PMID: 25402542 No abstract available.
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