title: Alogliptin after acute coronary syndrome in patients with type 2 diabetes.
abstract: BACKGROUND
  To assess potentially elevated cardiovascular risk related to new antihyperglycemic drugs in patients with type 2 diabetes, regulatory agencies require a comprehensive evaluation of the cardiovascular safety profile of new antidiabetic therapies. We assessed cardiovascular outcomes with alogliptin, a new inhibitor of dipeptidyl peptidase 4 (DPP-4), as compared with placebo in patients with type 2 diabetes who had had a recent acute coronary syndrome.
  
  
  METHODS
  We randomly assigned patients with type 2 diabetes and either an acute myocardial infarction or unstable angina requiring hospitalization within the previous 15 to 90 days to receive alogliptin or placebo in addition to existing antihyperglycemic and cardiovascular drug therapy. The study design was a double-blind, noninferiority trial with a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.
  
  
  RESULTS
  A total of 5380 patients underwent randomization and were followed for up to 40 months (median, 18 months). A primary end-point event occurred in 305 patients assigned to alogliptin (11.3%) and in 316 patients assigned to placebo (11.8%) (hazard ratio, 0.96; upper boundary of the one-sided repeated confidence interval, 1.16; P<0.001 for noninferiority). Glycated hemoglobin levels were significantly lower with alogliptin than with placebo (mean difference, -0.36 percentage points; P<0.001). Incidences of hypoglycemia, cancer, pancreatitis, and initiation of dialysis were similar with alogliptin and placebo.
  
  
  CONCLUSIONS
  Among patients with type 2 diabetes who had had a recent acute coronary syndrome, the rates of major adverse cardiovascular events were not increased with the DPP-4 inhibitor alogliptin as compared with placebo. (Funded by Takeda Development Center Americas; EXAMINE ClinicalTrials.gov number, NCT00968708.).
authors.affiliation: Calhoun Cardiology Center, Department of Medicine, University of Connecticut School of Medicine, 263 Farmington Ave., Farmington, CT 06030-3940, USA. wwhite@nso1.uchc.edu
authors.forename: William B
authors.initials: WB
authors.lastname: White
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.forename: Simon R
authors.initials: SR
authors.lastname: Heller
authors.forename: Steven E
authors.initials: SE
authors.lastname: Nissen
authors.forename: Richard M
authors.initials: RM
authors.lastname: Bergenstal
authors.forename: George L
authors.initials: GL
authors.lastname: Bakris
authors.forename: Alfonso T
authors.initials: AT
authors.lastname: Perez
authors.forename: Penny R
authors.initials: PR
authors.lastname: Fleck
authors.forename: Cyrus R
authors.initials: CR
authors.lastname: Mehta
authors.forename: Stuart
authors.initials: S
authors.lastname: Kupfer
authors.forename: Craig
authors.initials: C
authors.lastname: Wilson
authors.forename: William C
authors.initials: WC
authors.lastname: Cushman
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
mesh_terms: D000368:Aged; D000789:Angina, Unstable / Q000150:complications / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000401:mortality; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy*; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D014498:Uracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010880:Piperidines; D014498:Uracil; C520853:alogliptin