Hyperglycemia, particularly postprandial hyperglycemia, is thought to be an independent risk factor for cardiovascular disease in patients with diabetes. The STOP-Non-insulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial demonstrated that acarbose, an alpha-glucosidase inhibitor, decreased diabetes risk in patients with impaired glucose tolerance. Chiasson and colleagues also attempted to determine whether decreasing postprandial hyperglycemia would decrease the risk of hypertension and cardiovascular disease.

Male and female participants were 40 to 70 years of age and had a body mass index (BMI) between 25 and 40 kg per m². All had impaired glucose tolerance and a fasting blood glucose level between 100 and 140 mg per dL (5.5 and 7.8 mmol per L). Participants were randomized to placebo or to 100 mg of acarbose three times a day. All were instructed to follow a weight-reduction or a weight-maintenance diet and to exercise.

The main outcome measure was the occurrence of a major cardiovascular event, including heart disease. As a secondary objective, the effect of acarbose on the development of hypertension was observed. Glucose and lipid levels were followed. Analyses were adjusted for multiple variables, such as lipid levels, BMI, medications, and smoking.

Overall, 1,368 patients were randomized to receive acarbose (n = 682) or placebo (n = 686), with a mean follow-up of 3.3 years. Almost twice as many participants in the acarbose group (211 patients) discontinued the trial prematurely, mainly because of gastrointestinal side effects, compared with the placebo group (130 patients). There was no difference between the groups in terms of treatment or experience of cardiovascular disease at baseline. Acarbose therapy increased the probability that patients would remain free of cardiovascular events (hazard ratio of 0.51), with 32 in the placebo group and 15 in the acarbose group having at least one cardiovascular event. The relative risk reduction associated with acarbose therapy was 49 percent, and the absolute risk reduction was 2.5 percent. Besides acarbose treatment, other factors that positively correlated with cardiovascular events on univariate analysis included fasting plasma glucose levels, triglyceride concentrations, and systolic and diastolic blood pressures. Acarbose treatment lowered the risk of developing hypertension, with 78 patients (11 percent) developing hypertension in the acarbose group, compared with 115 (17 percent) in the placebo group, a relative risk reduction of 34 percent and an absolute risk reduction of 5.3 percent.

Acarbose was associated with a significant reduction in cardiovascular events in a group of participants with impaired glucose tolerance. In addition, acarbose reduced the risk of developing hypertension. The number needed to treat to prevent one case of hypertension in patients with impaired glucose tolerance would be 19 for 3.3 years. Although the reason for these risk reductions was not ascertained in the trial, it was observed that acarbose is associated with significant reductions in body weight and other risk factors related to the development of cardiovascular disease. On the basis of their trial results, the authors conclude that diabetes screening should identify patients with impaired glucose tolerance and that efforts should be made to reduce post-prandial hyperglycemia.