title: Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome.
abstract: BACKGROUND
  Cardiovascular morbidity and mortality are higher among patients with type 2 diabetes, particularly those with concomitant cardiovascular diseases, than in most other populations. We assessed the effects of lixisenatide, a glucagon-like peptide 1-receptor agonist, on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event.
  
  
  METHODS
  We randomly assigned patients with type 2 diabetes who had had a myocardial infarction or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined standards of care. The trial was designed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo, as defined by an upper boundary of the 95% confidence interval for the hazard ratio of less than 1.3 and 1.0, respectively, for the primary composite end point of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina.
  
  
  RESULTS
  The 6068 patients who underwent randomization were followed for a median of 25 months. A primary end-point event occurred in 406 patients (13.4%) in the lixisenatide group and in 399 (13.2%) in the placebo group (hazard ratio, 1.02; 95% confidence interval [CI], 0.89 to 1.17), which showed the noninferiority of lixisenatide to placebo (P<0.001) but did not show superiority (P=0.81). There were no significant between-group differences in the rate of hospitalization for heart failure (hazard ratio in the lixisenatide group, 0.96; 95% CI, 0.75 to 1.23) or the rate of death (hazard ratio, 0.94; 95% CI, 0.78 to 1.13). Lixisenatide was not associated with a higher rate of serious adverse events or severe hypoglycemia, pancreatitis, pancreatic neoplasms, or allergic reactions than was placebo.
  
  
  CONCLUSIONS
  In patients with type 2 diabetes and a recent acute coronary syndrome, the addition of lixisenatide to usual care did not significantly alter the rate of major cardiovascular events or other serious adverse events. (Funded by Sanofi; ELIXA ClinicalTrials.gov number, NCT01147250.).
authors.affiliation: From the Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (M.A.P., B.C., E.F.L., S.D.S.); Estudios Clínicos Latinoamérica, Rosario, Argentina (R.D.); University of Bergen, Stavanger University Hospital, Stavanger, Norway (K.D.); McMaster University, Hamilton, ON, Canada (H.C.G.); Rigshospitalet Copenhagen University Hospital, Copenhagen (L.V.K.); Sanofi U.S., Bridgewater, NJ (F.C.L., L.P., X.W.); Research Center of the Italian Association of Hospital Cardiologists, Florence (A.P.M.); British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (J.J.V.M.); University of Washington Medical Center, Seattle (J.L.P.); Oregon Health and Science University, Portland (M.C.R.); and Montreal Heart Institute, Université de Montréal, Montreal (J.C.T.).
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
authors.forename: Brian
authors.initials: B
authors.lastname: Claggett
authors.forename: Rafael
authors.initials: R
authors.lastname: Diaz
authors.forename: Kenneth
authors.initials: K
authors.lastname: Dickstein
authors.forename: Hertzel C
authors.initials: HC
authors.lastname: Gerstein
authors.forename: Lars V
authors.initials: LV
authors.lastname: Køber
authors.forename: Francesca C
authors.initials: FC
authors.lastname: Lawson
authors.forename: Lin
authors.initials: L
authors.lastname: Ping
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Wei
authors.forename: Eldrin F
authors.initials: EF
authors.lastname: Lewis
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Probstfield
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Riddle
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications / Q000188:drug therapy*; D000368:Aged; D000789:Angina, Unstable / Q000150:complications; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D017211:Treatment Failure; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010455:Peptides; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor