title: Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6).
abstract: BACKGROUND
  Unlike most antihyperglycaemic drugs, glucagon-like peptide-1 (GLP-1) receptor agonists have a glucose-dependent action and promote weight loss. We compared the efficacy and safety of liraglutide, a human GLP-1 analogue, with exenatide, an exendin-based GLP-1 receptor agonist.
  
  
  METHODS
  Adults with inadequately controlled type 2 diabetes on maximally tolerated doses of metformin, sulphonylurea, or both, were stratified by previous oral antidiabetic therapy and randomly assigned to receive additional liraglutide 1.8 mg once a day (n=233) or exenatide 10 microg twice a day (n=231) in a 26-week open-label, parallel-group, multinational (15 countries) study. The primary outcome was change in glycosylated haemoglobin (HbA(1c)). Efficacy analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00518882.
  
  
  RESULTS
  Mean baseline HbA(1c) for the study population was 8.2%. Liraglutide reduced mean HbA(1c) significantly more than did exenatide (-1.12% [SE 0.08] vs -0.79% [0.08]; estimated treatment difference -0.33; 95% CI -0.47 to -0.18; p<0.0001) and more patients achieved a HbA(1c) value of less than 7% (54%vs 43%, respectively; odds ratio 2.02; 95% CI 1.31 to 3.11; p=0.0015). Liraglutide reduced mean fasting plasma glucose more than did exenatide (-1.61 mmol/L [SE 0.20] vs -0.60 mmol/L [0.20]; estimated treatment difference -1.01 mmol/L; 95% CI -1.37 to -0.65; p<0.0001) but postprandial glucose control was less effective after breakfast and dinner. Both drugs promoted similar weight losses (liraglutide -3.24 kg vs exenatide -2.87 kg). Both drugs were well tolerated, but nausea was less persistent (estimated treatment rate ratio 0.448, p<0.0001) and minor hypoglycaemia less frequent with liraglutide than with exenatide (1.93 vs 2.60 events per patient per year; rate ratio 0.55; 95% CI 0.34 to 0.88; p=0.0131; 25.5%vs 33.6% had minor hypoglycaemia). Two patients taking both exenatide and a sulphonylurea had a major hypoglycaemic episode.
  
  
  CONCLUSIONS
  Liraglutide once a day provided significantly greater improvements in glycaemic control than did exenatide twice a day, and was generally better tolerated. The results suggest that liraglutide might be a treatment option for type 2 diabetes, especially when weight loss and risk of hypoglycaemia are major considerations.
  
  
  BACKGROUND
  Novo Nordisk A/S.
authors.affiliation: Division of Endocrinology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. jbuse@med.unc.edu
authors.forename: John B
authors.initials: JB
authors.lastname: Buse
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sesti
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Schmidt
authors.forename: Eduard
authors.initials: E
authors.lastname: Montanya
authors.forename: Jason H
authors.initials: JH
authors.lastname: Brett
authors.forename: Marcin
authors.initials: M
authors.lastname: Zychma
authors.forename: Lawrence
authors.initials: L
authors.lastname: Blonde
mesh_terms: D000704:Analysis of Variance; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000819:agonists / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D016014:Linear Models; D000069450:Liraglutide; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010455:Peptides / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D016896:Treatment Outcome; D014688:Venoms / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D015431:Weight Loss / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D010455:Peptides; D014688:Venoms