title: Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus.
abstract: BACKGROUND
  The cardiovascular safety and efficacy of many current antihyperglycemic agents, including saxagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, are unclear.
  
  
  METHODS
  We randomly assigned 16,492 patients with type 2 diabetes who had a history of, or were at risk for, cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years. Physicians were permitted to adjust other medications, including antihyperglycemic agents. The primary end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke.
  
  
  RESULTS
  A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group (7.3% and 7.2%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio with saxagliptin, 1.00; 95% confidence interval [CI], 0.89 to 1.12; P=0.99 for superiority; P<0.001 for noninferiority); the results were similar in the "on-treatment" analysis (hazard ratio, 1.03; 95% CI, 0.91 to 1.17). The major secondary end point of a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group (12.8% and 12.4%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio, 1.02; 95% CI, 0.94 to 1.11; P=0.66). More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure (3.5% vs. 2.8%; hazard ratio, 1.27; 95% CI, 1.07 to 1.51; P=0.007). Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups (acute pancreatitis, 0.3% in the saxagliptin group and 0.2% in the placebo group; chronic pancreatitis, <0.1% and 0.1% in the two groups, respectively).
  
  
  CONCLUSIONS
  DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events, though the rate of hospitalization for heart failure was increased. Although saxagliptin improves glycemic control, other approaches are necessary to reduce cardiovascular risk in patients with diabetes. (Funded by AstraZeneca and Bristol-Myers Squibb; SAVOR-TIMI 53 ClinicalTrials.gov number, NCT01107886.).
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, USA.
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: P 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: Robert
authors.initials: R
authors.lastname: Frederich
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Wiviott
authors.forename: Elaine B
authors.initials: EB
authors.lastname: Hoffman
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cavender
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Udell
authors.forename: Nihar R
authors.initials: NR
authors.lastname: Desai
authors.forename: Ofri
authors.initials: O
authors.lastname: Mosenzon
authors.forename: Darren K
authors.initials: DK
authors.lastname: McGuire
authors.forename: Kausik K
authors.initials: KK
authors.lastname: Ray
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Leiter
authors.forename: Itamar
authors.initials: I
authors.lastname: Raz
mesh_terms: D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000209:etiology / Q000401:mortality; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004151:Dipeptides / Q000009:adverse effects / Q000627:therapeutic use*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000453:epidemiology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; C502994:saxagliptin; D000218:Adamantane