title: Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes.
abstract: BACKGROUND
  Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease.
  
  
  METHODS
  In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina.
  
  
  RESULTS
  During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P=0.98). There were no significant between-group differences in rates of acute pancreatitis (P=0.07) or pancreatic cancer (P=0.32).
  
  
  CONCLUSIONS
  Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events. (Funded by Merck Sharp & Dohme; TECOS ClinicalTrials.gov number, NCT00790205.).
authors.affiliation: From the Duke Clinical Research Institute, Duke University School of Medicine, Durham (J.B.G., J.G., M.J.P., E.D.P.) and University of North Carolina School of Medicine, Chapel Hill (J.B.B.) - both in North Carolina; Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom (M.A.B., R.R.H.); Canadian VIGOUR Centre, University of Alberta, Edmonton, AB (P.W.A.) and St. Michael's Hospital, University of Toronto, Toronto (R.J.) - both in Canada; Merck, Kenilworth, NJ (S.S.E., K.D.K., J.K., S.K., P.P.S., S.S.); George Washington University Biostatistics Center, Rockville, MD (J.M.L.); University of Texas Southwestern Medical Center, Dallas (D.K.M.); Munich Diabetes Research Group, Helmholtz Center, Neuherberg, Germany (E.S.); and University of Leuven, Leuven, Belgium (F.V.W.).
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Green
authors.forename: M Angelyn
authors.initials: MA
authors.lastname: Bethel
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.forename: John B
authors.initials: JB
authors.lastname: Buse
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Engel
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Garg
authors.forename: Robert
authors.initials: R
authors.lastname: Josse
authors.forename: Keith D
authors.initials: KD
authors.lastname: Kaufman
authors.forename: Joerg
authors.initials: J
authors.lastname: Koglin
authors.forename: Scott
authors.initials: S
authors.lastname: Korn
authors.forename: John M
authors.initials: JM
authors.lastname: Lachin
authors.forename: Darren K
authors.initials: DK
authors.lastname: McGuire
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pencina
authors.forename: Eberhard
authors.initials: E
authors.lastname: Standl
authors.forename: Peter P
authors.initials: PP
authors.lastname: Stein
authors.forename: Shailaja
authors.initials: S
authors.lastname: Suryawanshi
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.forename: Eric D
authors.initials: ED
authors.lastname: Peterson
authors.forename: Rury R
authors.initials: RR
authors.lastname: Holman
mesh_terms: D000284:Administration, Oral; D002318:Cardiovascular Diseases / Q000150:complications* / Q000401:mortality; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006331:Heart Diseases / Q000453:epidemiology / Q000209:etiology; D006333:Heart Failure / Q000209:etiology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D011719:Pyrazines / Q000009:adverse effects* / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D014230:Triazoles; C517652:hemoglobin A1c protein, human