title: Effect of ramipril on the incidence of diabetes.
abstract: BACKGROUND
  Previous studies have suggested that blockade of the renin-angiotensin system may prevent diabetes in people with cardiovascular disease or hypertension.
  
  
  METHODS
  In a double-blind, randomized clinical trial with a 2-by-2 factorial design, we randomly assigned 5269 participants without cardiovascular disease but with impaired fasting glucose levels (after an 8-hour fast) or impaired glucose tolerance to receive ramipril (up to 15 mg per day) or placebo (and rosiglitazone or placebo) and followed them for a median of 3 years. We studied the effects of ramipril on the development of diabetes or death, whichever came first (the primary outcome), and on secondary outcomes, including regression to normoglycemia.
  
  
  RESULTS
  The incidence of the primary outcome did not differ significantly between the ramipril group (18.1%) and the placebo group (19.5%; hazard ratio for the ramipril group, 0.91; 95% confidence interval [CI], 0.81 to 1.03; P=0.15). Participants receiving ramipril were more likely to have regression to normoglycemia than those receiving placebo (hazard ratio, 1.16; 95% CI, 1.07 to 1.27; P=0.001). At the end of the study, the median fasting plasma glucose level was not significantly lower in the ramipril group (102.7 mg per deciliter [5.70 mmol per liter]) than in the placebo group (103.4 mg per deciliter [5.74 mmol per liter], P=0.07), though plasma glucose levels 2 hours after an oral glucose load were significantly lower in the ramipril group (135.1 mg per deciliter [7.50 mmol per liter] vs. 140.5 mg per deciliter [7.80 mmol per liter], P=0.01).
  
  
  CONCLUSIONS
  Among persons with impaired fasting glucose levels or impaired glucose tolerance, the use of ramipril for 3 years does not significantly reduce the incidence of diabetes or death but does significantly increase regression to normoglycemia. (ClinicalTrials.gov number, NCT00095654 [ClinicalTrials.gov].).
authors.affiliation: McMaster University, Hamilton, Canada.
authors.forename: Jackie
authors.initials: J
authors.lastname: Bosch
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Hertzel C
authors.initials: HC
authors.lastname: Gerstein
authors.forename: Janice
authors.initials: J
authors.lastname: Pogue
authors.forename: Patrick
authors.initials: P
authors.lastname: Sheridan
authors.forename: Gilles
authors.initials: G
authors.lastname: Dagenais
authors.forename: Rafael
authors.initials: R
authors.lastname: Diaz
authors.forename: Alvaro
authors.initials: A
authors.lastname: Avezum
authors.forename: Fernando
authors.initials: F
authors.lastname: Lanas
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Probstfield
authors.forename: George
authors.initials: G
authors.lastname: Fodor
authors.forename: Rury R
authors.initials: RR
authors.lastname: Holman
mesh_terms: D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects*; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000517:prevention & control*; D004311:Double-Blind Method; D005215:Fasting / Q000097:blood; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D017257:Ramipril / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D017257:Ramipril