title: Adding liraglutide to oral antidiabetic drug therapy: onset of treatment effects over time.
abstract: OBJECTIVE
  To investigate the onset of treatment effects over time observed for liraglutide in combination with oral antidiabetic drugs (OADs).
  
  
  METHODS
  This analysis included patients from three phase 3, 26-week, randomised, double-blind, parallel-group trials. Prior to randomisation, patients underwent a run-in and titration period with metformin (Liraglutide Effect and Action in Diabetes-2, LEAD-2), glimepiride (LEAD-1) or metformin plus rosiglitazone (LEAD-4). Patients were then randomised to receive liraglutide (0.6, 1.2 or 1.8 mg once-daily), active comparator and/or placebo. For this analysis, only the 1.2 mg and 1.8 mg liraglutide doses were included. Outcome measures included change in HbA(1c), fasting plasma glucose (FPG), weight and systolic blood pressure (SBP). The safety profile was also investigated.
  
  
  RESULTS
  Significant reductions in HbA(1c) were observed within 8 weeks of treatment with liraglutide plus OADs (p < 0.0001) and maintained until week 26. Furthermore, liraglutide plus OADs led to significant reductions in FPG within 2 weeks (p < 0.0001) and sustained over 26 weeks. Adding liraglutide to metformin or metformin plus rosiglitazone also led to early reductions and maintained reductions in body weight (within 8 weeks, p < 0.0001); however, liraglutide treatment plus glimepiride was weight neutral. Rapid reductions in SBP were observed for liraglutide plus OADs (within 2 weeks, p < 0.05-0.001) and maintained for 26 weeks. Some patients experienced nausea, which for the majority it diminished within 2 weeks.
  
  
  CONCLUSIONS
  Liraglutide treatment combined with OADs led to rapid improvements in FPG and SBP. Early reductions in HbA(1c) and body weight were also observed. Adding liraglutide to OADs early on may therefore be a good treatment option for patients with type 2 diabetes.
authors.affiliation: Department of Medicine IV, University Hospital of Tübingen, Tübingen, Germany. baptist.gallwitz@med.unituebingen.de
authors.forename: B
authors.initials: B
authors.lastname: Gallwitz
authors.forename: A
authors.initials: A
authors.lastname: Vaag
authors.forename: A
authors.initials: A
authors.lastname: Falahati
authors.forename: S
authors.initials: S
authors.lastname: Madsbad
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005215:Fasting / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D000069450:Liraglutide; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069450:Liraglutide