title: Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial.
abstract: BACKGROUND
  Agonists of the glucagon-like peptide-1 (GLP-1) receptor provide pharmacological levels of GLP-1 activity, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors increase concentrations of endogenous GLP-1 and glucose-dependent insulinotropic polypeptide. We aimed to assess the efficacy and safety of the human GLP-1 analogue liraglutide versus the DPP-4 inhibitor sitagliptin, as adjunct treatments to metformin, in individuals with type 2 diabetes who did not achieve adequate glycaemic control with metformin alone.
  
  
  METHODS
  In this parallel-group, open-label trial, participants (aged 18-80 years) with type 2 diabetes mellitus who had inadequate glycaemic control (glycosylated haemoglobin [HbA(1c)] 7.5-10.0%) on metformin (>or=1500 mg daily for >or=3 months) were enrolled and treated at office-based sites in Europe, the USA, and Canada. Participants were randomly allocated to receive 26 weeks' treatment with 1.2 mg (n=225) or 1.8 mg (n=221) subcutaneous liraglutide once daily, or 100 mg oral sitagliptin once daily (n=219). The primary endpoint was change in HbA(1c) from baseline to week 26. The efficacy of liraglutide versus sitagliptin was assessed hierarchically by a non-inferiority comparison, with a margin of 0.4%, followed by a superiority comparison. Analyses were done on the full analysis set with missing values imputed by last observation carried forward; seven patients assigned to liraglutide did not receive treatment and thus did not meet criteria for inclusion in the full analysis set. This trial is registered with ClinicalTrials.gov, number NCT00700817.
  
  
  RESULTS
  Greater lowering of mean HbA(1c) (8.5% at baseline) was achieved with 1.8 mg liraglutide (-1.50%, 95% CI -1.63 to -1.37, n=218) and 1.2 mg liraglutide (-1.24%, -1.37 to -1.11, n=221) than with sitagliptin (-0.90%, -1.03 to -0.77, n=219). Estimated mean treatment differences for liraglutide versus sitagliptin were -0.60% (95% CI -0.77 to -0.43, p<0.0001) for 1.8 mg and -0.34% (-0.51 to -0.16, p<0.0001) for 1.2 mg liraglutide. Nausea was more common with liraglutide (59 [27%] patients on 1.8 mg; 46 [21%] on 1.2 mg) than with sitagliptin (10 [5%]). Minor hypoglycaemia was recorded in about 5% of participants in each treatment group.
  
  
  CONCLUSIONS
  Liraglutide was superior to sitagliptin for reduction of HbA(1c), and was well tolerated with minimum risk of hypoglycaemia. These findings support the use of liraglutide as an effective GLP-1 agent to add to metformin.
  
  
  BACKGROUND
  Novo Nordisk.
authors.affiliation: Diabetes and Metabolism Translational Medicine Unit, University of Vermont College of Medicine, Burlington, VT, USA. richard.pratley@uvm.edu
authors.forename: Richard E
authors.initials: RE
authors.lastname: Pratley
authors.forename: Michael
authors.initials: M
authors.lastname: Nauck
authors.forename: Timothy
authors.initials: T
authors.lastname: Bailey
authors.forename: Eduard
authors.initials: E
authors.lastname: Montanya
authors.forename: Robert
authors.initials: R
authors.lastname: Cuddihy
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Filetti
authors.forename: Anne Bloch
authors.initials: AB
authors.lastname: Thomsen
authors.forename: Rie Elvang
authors.initials: RE
authors.lastname: Søndergaard
authors.forename: Melanie
authors.initials: M
authors.lastname: Davies
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069450:Liraglutide; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D011719:Pyrazines / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D017211:Treatment Failure; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D011719:Pyrazines; D014230:Triazoles; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D008687:Metformin; D000068900:Sitagliptin Phosphate