First published in The Lancet on 2014 Oct
JLancet. 2014 Oct 11;384(9951):1349-57. doi: 10.1016/S0140-6736(14)60976-4. Epub 2014 Jul 10
Authors: Dungan KM, Povedano ST, Forst T, González JG, Atisso C, Sealls W, Fahrbach JL
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/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.
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.
In summary, large volume and thigh injections are rated more Once-weekly dulaglutide is non-inferior to once-daily liraglutide for least-squares mean reduction in HbA1c, with a similar safety and tolerability profile.