title: The design and rationale of the saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus-thrombolysis in myocardial infarction (SAVOR-TIMI) 53 study.
abstract: OBJECTIVE
  Saxagliptin, a dipeptidyl peptidase 4 inhibitor, improves glycemic control in patients with type 2 diabetes mellitus (T2DM) by increasing endogenous active, intact glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide in response to food, which augments insulin secretion and decreases glucagon release.
  
  
  METHODS
  SAVOR-TIMI 53 is a phase 4, randomized, double-blind, placebo-controlled trial conducted in 25 countries that is designed to evaluate the safety and efficacy of saxagliptin during long-term treatment of approximately 16,500 patients with T2DM. Eligible patients who are either treatment naive or on any background antidiabetic treatment (except incretin therapy) with history of established cardiovascular (CV) disease or multiple risk factors are randomized 1:1 to saxagliptin 5 mg QD (2.5 mg in subjects with moderate/severe renal impairment) or matching placebo, stratified by qualifying disease state. The primary end point is the composite of CV death, nonfatal myocardial infarction, or nonfatal ischemic stroke. The trial will continue until approximately 1,040 primary end points accrue, providing 85% power to identify a 17% relative reduction of the primary end point with saxagliptin versus placebo and 98% power to test for noninferiority of saxagliptin versus placebo (reject the upper limit of 95% CI for a hazard ratio <1.3 at a 1-sided α of .025).
  
  
  CONCLUSIONS
  SAVOR-TIMI 53 is testing the hypothesis that treatment with saxagliptin is safe and reduces CV events in high-risk patients with T2DM.
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. bscirica@partners.org
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Scirica
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.forename: Ph Gabriel
authors.initials: PG
authors.lastname: Steg
authors.forename: Jaime
authors.initials: J
authors.lastname: Davidson
authors.forename: Boaz
authors.initials: B
authors.lastname: Hirshberg
authors.forename: Peter
authors.initials: P
authors.lastname: Ohman
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Price
authors.forename: Roland
authors.initials: R
authors.lastname: Chen
authors.forename: Jacob
authors.initials: J
authors.lastname: Udell
authors.forename: Itamar
authors.initials: I
authors.lastname: Raz
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004151:Dipeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005602:France; D006801:Humans; D007557:Israel; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications* / Q000401:mortality; D012107:Research Design; D016019:Survival Analysis; D016896:Treatment Outcome; D014481:United States
chemical_list: D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; C502994:saxagliptin; D000218:Adamantane