title: Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial.
abstract: BACKGROUND
  Diabetes is a multisystem disorder associated with a nearly twofold excess risk for a broad range of adverse cardiovascular outcomes including coronary heart disease, stroke, and cardiovascular death. Liraglutide is a human glucagon-like peptide receptor analog approved for use in patients with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  To formally assess the cardiovascular safety of liraglutide, the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial was commenced in 2010. LEADER is a phase 3B, multicenter, international, randomized, double-blind, placebo-controlled clinical trial with long-term follow-up. Patients with T2DM at high risk for cardiovascular disease (CVD) who were either drug naive or treated with oral antihyperglycemic agents or selected insulin regimens (human NPH, long-acting analog, or premixed) alone or in combination with oral antihyperglycemics were eligible for inclusion. Randomized patients are being followed for up to 5 years. The primary end point is the time from randomization to a composite outcome consisting of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
  
  
  CONCLUSIONS
  LEADER commenced in September 2010, and enrollment concluded in April 2012. There were 9,340 patients enrolled at 410 sites in 32 countries. The mean age of patients was 64.3 ± 7.2 years, 64.3% were men, and mean body mass index was 32.5 ± 6.3 kg/m2. There were 7,592 (81.3%) patients with prior CVD and 1,748 (18.7%) who were high risk but without prior CVD. It is expected that LEADER will provide conclusive data regarding the cardiovascular safety of liraglutide relative to the current standard of usual care for a global population of patients with T2DM.
authors.affiliation: Saint Luke's Mid America Heart Institute, Kansas City, Missouri. Electronic address: smarso@saint-lukes.org.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Marso
authors.forename: Neil R
authors.initials: NR
authors.lastname: Poulter
authors.forename: Steven E
authors.initials: SE
authors.lastname: Nissen
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nauck
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.forename: Gilbert H
authors.initials: GH
authors.lastname: Daniels
authors.forename: Stuart
authors.initials: S
authors.lastname: Pocock
authors.forename: William M
authors.initials: WM
authors.lastname: Steinberg
authors.forename: Richard M
authors.initials: RM
authors.lastname: Bergenstal
authors.forename: Johannes F E
authors.initials: JF
authors.lastname: Mann
authors.forename: Lasse Steen
authors.initials: LS
authors.lastname: Ravn
authors.forename: Kirstine Brown
authors.initials: KB
authors.lastname: Frandsen
authors.forename: Alan C
authors.initials: AC
authors.lastname: Moses
authors.forename: John B
authors.initials: JB
authors.lastname: Buse
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1