title: Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study.
abstract: BACKGROUND
  Glucagon-like peptide-1 receptor agonists exenatide and liraglutide have been shown to improve glycaemic control and reduce bodyweight in patients with type 2 diabetes. We compared the efficacy and safety of exenatide once weekly with liraglutide once daily in patients with type 2 diabetes.
  
  
  METHODS
  We did a 26 week, open-label, randomised, parallel-group study at 105 sites in 19 countries between Jan 11, 2010, and Jan 17, 2011. Patients aged 18 years or older with type 2 diabetes treated with lifestyle modification and oral antihyperglycaemic drugs were randomly assigned (1:1), via a computer-generated randomisation sequence with a voice response system, to receive injections of once-daily liraglutide (1·8 mg) or once-weekly exenatide (2 mg). Participants and investigators were not masked to treatment assignment. The primary endpoint was change in glycated haemoglobin (HbA(1c)) from baseline to week 26. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01029886.
  
  
  RESULTS
  Of 912 randomised patients, 911 were included in the intention-to-treat analysis (450 liraglutide, 461 exenatide). The least-squares mean change in HbA(1c) was greater in patients in the liraglutide group (-1·48%, SE 0·05; n=386) than in those in the exenatide group (-1·28%, 0·05; 390) with the treatment difference (0·21%, 95% CI 0·08-0·33) not meeting predefined non-inferiority criteria (upper limit of CI <0·25%). The most common adverse events were nausea (93 [21%] in the liraglutide group vs 43 [9%] in the exenatide group), diarrhoea (59 [13%] vs 28 [6%]), and vomiting 48 [11%] vs 17 [4%]), which occurred less frequently in the exenatide group and with decreasing incidence over time in both groups. 24 (5%) patients allocated to liraglutide and 12 (3%) allocated to exenatide discontinued participation because of adverse events.
  
  
  CONCLUSIONS
  Both once daily liraglutide and once weekly exenatide led to improvements in glycaemic control, with greater reductions noted with liraglutide. These findings, plus differences in injection frequency and tolerability, could inform therapeutic decisions for treatment of patients with type 2 diabetes.
  
  
  BACKGROUND
  Eli Lilly and Company and Amylin Pharmaceuticals LLC.
authors.affiliation: University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Buse
authors.forename: Michael
authors.initials: M
authors.lastname: Nauck
authors.forename: Thomas
authors.initials: T
authors.lastname: Forst
authors.forename: Wayne H-H
authors.initials: WH
authors.lastname: Sheu
authors.forename: Sylvia K
authors.initials: SK
authors.lastname: Shenouda
authors.forename: Cory R
authors.initials: CR
authors.lastname: Heilmann
authors.forename: Byron J
authors.initials: BJ
authors.lastname: Hoogwerf
authors.forename: Aijun
authors.initials: A
authors.lastname: Gao
authors.forename: Marilyn K
authors.initials: MK
authors.lastname: Boardman
authors.forename: Mark
authors.initials: M
authors.lastname: Fineman
authors.forename: Lisa
authors.initials: L
authors.lastname: Porter
authors.forename: Guntram
authors.initials: G
authors.lastname: Schernthaner
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004334:Drug Administration Schedule; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014688:Venoms / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D010455:Peptides; D014688:Venoms; C517652:hemoglobin A1c protein, human