Ramipril and the development of diabetes.
BACKGROUND
Type 2 diabetes is a growing clinical and public health problem. Preventive efforts related to lifestyle modification are not always successful; therefore, alternative prevention strategies need to be studied.


OBJECTIVE
To investigate the effectiveness of ramipril, an angiotensin-converting enzyme inhibitor, in preventing diabetes among high-risk persons.


METHODS
The randomized, controlled Heart Outcomes Prevention Evaluation trial of 5720 patients older than 55 years without known diabetes but with vascular disease who were followed up for a mean of 4.5 years. The study included 267 hospitals in 19 countries and was conducted between 1994 and 1999.


METHODS
Patients were randomly assigned to receive ramipril, up to 10 mg/d (n = 2837), or placebo (n = 2883).


METHODS
Diagnosis of diabetes determined from self-report at follow-up visits every 6 months, compared between the 2 groups.


RESULTS
One hundred and two individuals (3.6%) in the ramipril group developed diabetes compared with 155 (5.4%) in the placebo group (relative risk [RR], 0.66; 95% confidence interval [CI], 0.51-0.85, P<.001). Similar results were noted when different diagnostic criteria were used; in the ramipril group, the RR for diagnosis of diabetes and hemoglobin A(1c) greater than 110% was 0.60 (95% CI, 0.43-0.85), for initiation of glucose-lowering therapy, 0.56 (95% CI, 0.41-0.77), and for both, 0.51 (95% CI, 0.34-0.76). These effects were also consistently seen in several subgroups examined.


CONCLUSIONS
Ramipril is associated with lower rates of new diagnosis of diabetes in high-risk individuals. Because these results have important clinical and public health implications, this hypothesis requires prospective confirmation.
Yusuf
S
S
Canadian Cardiovascular Collaboration Project Office, Hamilton General Hospital, 237 Barton St East, Hamilton, Ontario, Canada L8L 2X2. yusufs@mcmaster.ca
Gerstein
H
H
Hoogwerf
B
B
Pogue
J
J
Bosch
J
J
Wolffenbuttel
B H
BH
Zinman
B
B
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy; D003920:Diabetes Mellitus / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D017257:Ramipril / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis
D000806:Angiotensin-Converting Enzyme Inhibitors; D017257:Ramipril