title: Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study.
abstract: OBJECTIVE
  The impact of insulin secretagogues (ISs) on long-term major clinical outcomes in type 2 diabetes remains unclear. We examined mortality and cardiovascular risk associated with all available ISs compared with metformin in a nationwide study.
  
  
  RESULTS
  All Danish residents >20 years, initiating single-agent ISs or metformin between 1997 and 2006 were followed for up to 9 years (median 3.3 years) by individual-level linkage of nationwide registers. All-cause mortality, cardiovascular mortality, and the composite of myocardial infarction (MI), stroke, and cardiovascular mortality associated with individual ISs were investigated in patients with or without previous MI by multivariable Cox proportional-hazard analyses including propensity analyses. A total of 107 806 subjects were included, of whom 9607 had previous MI. Compared with metformin, glimepiride (hazard ratios and 95% confidence intervals): 1.32 (1.24-1.40), glibenclamide: 1.19 (1.11-1.28), glipizide: 1.27 (1.17-1.38), and tolbutamide: 1.28 (1.17-1.39) were associated with increased all-cause mortality in patients without previous MI. The corresponding results for patients with previous MI were as follows: glimepiride: 1.30 (1.11-1.44), glibenclamide: 1.47 (1.22-1.76), glipizide: 1.53 (1.23-1.89), and tolbutamide: 1.47 (1.17-1.84). Results for gliclazide [1.05 (0.94-1.16) and 0.90 (0.68-1.20)] and repaglinide and [0.97 (0.81-1.15) and 1.29 (0.86-1.94)] were not statistically different from metformin in both patients without and with previous MI, respectively. Results were similar for cardiovascular mortality and for the composite endpoint.
  
  
  CONCLUSIONS
  Monotherapy with the most used ISs, including glimepiride, glibenclamide, glipizide, and tolbutamide, seems to be associated with increased mortality and cardiovascular risk compared with metformin. Gliclazide and repaglinide appear to be associated with a lower risk than other ISs.
authors.affiliation: Department of Cardiology B, section 2141, Rigshospitalet, The Heart Center, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark. tks@heart.dk
authors.forename: Tina Ken
authors.initials: TK
authors.lastname: Schramm
authors.forename: Gunnar Hilmar
authors.initials: GH
authors.lastname: Gislason
authors.forename: Allan
authors.initials: A
authors.lastname: Vaag
authors.forename: Jeppe Nørgaard
authors.initials: JN
authors.lastname: Rasmussen
authors.forename: Fredrik
authors.initials: F
authors.lastname: Folke
authors.forename: Morten Lock
authors.initials: ML
authors.lastname: Hansen
authors.forename: Emil Loldrup
authors.initials: EL
authors.lastname: Fosbøl
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.forename: Mette Lykke
authors.initials: ML
authors.lastname: Norgaard
authors.forename: Mette
authors.initials: M
authors.lastname: Madsen
authors.forename: Peter Riis
authors.initials: PR
authors.lastname: Hansen
authors.forename: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
mesh_terms: D000328:Adult; D000368:Aged; D002423:Cause of Death; D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000401:mortality; D003925:Diabetic Angiopathies / Q000401:mortality*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000031:analogs & derivatives*; D053208:Kaplan-Meier Estimate; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality*; D012307:Risk Factors; D020521:Stroke / Q000401:mortality; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin