The worldwide explosive increase in type 2 diabetes mellitus and its
cardiovascular morbidity are becoming major health concerns.
To evaluate the effect of decreasing postprandial hyperglycemia with
acarbose, an α-glucosidase inhibitor, on the risk of cardiovascular
disease and hypertension in patients with impaired glucose tolerance (IGT).
Design, Setting, and Participants
International, multicenter double-blind, placebo-controlled, randomized
trial, undertaken in hospitals in Canada, Germany, Austria, Norway, Denmark,
Sweden, Finland, Israel, and Spain from July 1998 through August 2001. A total
of 1429 patients with IGT were randomized with 61 patients (4%) excluded because
they did not have IGT or had no postrandomization data, leaving 1368 patients
for a modified intent-to-treat analysis. Both men (49%) and women (51%) participated
with a mean (SD) age of 54.5 (7.9) years and body mass index of 30.9 (4.2).
These patients were followed up for a mean (SD) of 3.3 (1.2) years.
Patients with IGT were randomized to receive either placebo (n = 715)
or 100 mg of acarbose 3 times a day (n = 714).
Main Outcome Measures
The development of major cardiovascular events (coronary heart disease,
cardiovascular death, congestive heart failure, cerebrovascular event, and
peripheral vascular disease) and hypertension (≥140/90 mm Hg).
Three hundred forty-one patients (24%) discontinued their participation
prematurely, 211 in the acarbose-treated group and 130 in the placebo group;
these patients were also followed up for outcome parameters. Decreasing postprandial
hyperglycemia with acarbose was associated with a 49% relative risk reduction
in the development of cardiovascular events (hazard ratio [HR], 0.51; 95%
confidence interval [CI]; 0.28-0.95; P = .03) and
a 2.5% absolute risk reduction. Among cardiovascular events, the major reduction
was in the risk of myocardial infarction (HR, 0.09; 95% CI, 0.01-0.72; P = .02). Acarbose was also associated with a 34% relative
risk reduction in the incidence of new cases of hypertension (HR, 0.66; 95%
CI, 0.49-0.89; P = .006) and a 5.3% absolute risk
reduction. Even after adjusting for major risk factors, the reduction in the
risk of cardiovascular events (HR, 0.47; 95% CI, 0.24-0.90; P = .02) and hypertension (HR, 0.62; 95% CI, 0.45-0.86; P = .004) associated with acarbose treatment was still statistically
This study suggests that treating IGT patients with acarbose is associated
with a significant reduction in the risk of cardiovascular disease and hypertension.