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Study TO Prevent Noninsulin Dependent Diabetes Mellitus trial - STOP-NIDDM
Description:
The goal of the STOP-NIDDM trial was to evaluate the effect of decreasing postprandial hyperglycemia with acarbose, an alpha-glucosidase inhibitor, on the risk of diabetes, cardiovascular (CV) disease, and hypertension in patients with impaired glucose tolerance (IGT).
Study Design
Study Design:
Patients Screened: 14,742
Patients Enrolled: 1,429
Mean Follow Up: Mean follow-up of 3.3 years
Mean Patient Age: Mean age 54.5 years
Female: 51
Patient Populations:
Age 40-70 years; body mass index (BMI) between 25 and 40; and IGT according to the World Health Organization criteria, plus a fasting plasma glucose concentration of between 100 and 140 mg/dl
Exclusions:
Any CV event within the last six months
Primary Endpoints:
Development of diabetes
Secondary Endpoints:
Major CV events, including coronary heart disease (MI, new angina, revascularization procedures), CV death, congestive heart failure, cerebrovascular events, and peripheral vascular disease; and development of new cases of hypertension
Drug/Procedures Used:
Patients were randomized to placebo (n=686) or 100 mg of acarbose three times/day (n=682), taken with the first bite of each meal. Patients were instructed to go on a weight-reduction or weight-maintenance diet, and were encouraged to exercise regularly.
Principal Findings:
Treatment was discontinued prematurely in 211 patients in the acarbose arm and in 130 patients in the placebo arm, with the most common reason adverse gastrointestinal tract effects. Diabetes developed less frequently in the acarbose arm compared with placebo (32% vs. 42%, hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.63-0.90, p=0.0015). Acarbose also significantly increased the percentage of patients returning from IGT to normal glucose tolerance (p<0.0001).
Fewer CV events occurred in the acarbose arm than the placebo arm (15 events vs. 32 events; HR 0.51, 95% CI 0.28-0.95; p=0.03). Among the components of the CV events, the major reduction was myocardial infarction (MI) (1 MI vs. 12 MIs; HR 0.09, 95% CI 0.01-0.72, p=0.02), with no significant difference in angina (HR 0.45, 95% CI 0.16-1.28, p=0.13), revascularization (HR 0.61, 95% CI 0.29-1.26, p=0.18), or CV death (HR 0.55, 95% CI 0.05-6.11, p=0.63).
Acarbose remained associated with a reduction in CV events even after adjusting for major risk factors, including fasting plasma glucose levels and systolic blood pressure (HR, 0.47, 95% CI 0.24-0.90, p=0.02). Development of hypertension occurred less frequently in the acarbose group (11% vs. 17%, HR 0.66, 95% CI 0.49-0.89, p=0.006), and remained significant after multivariate adjustment (HR 0.62, 95% CI 0.45-0.86, p=0.004).
Interpretation:
Among patients with IGT, treatment with the alpha-glucosidase inhibitor acarbose was associated with a reduction in the development of diabetes, and CV events compared with placebo. Previous trials have demonstrated that changes in lifestyle are effective in the prevention of type 2 diabetes. However, few have examined the use of pharmacological therapy in addition to exercise and diet for prevention of diabetes.
The authors suggest the mechanism for the reduction in development of diabetes may be due to the ability of acarbose to significantly decrease the postprandial rise in plasma glucose. Prior studies have demonstrated that the higher the two-hour plasma glucose concentration after a glucose load in patients with impaired glucose tolerance, the higher the conversion rate to diabetes.
References:
Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 2002;359:2072-7.
Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M, for the STOP-NIDDM Trial Research Group. Acarbose Treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA 2003;290:486-94.
Presented at the European Society of Cardiology Congress, Vienna, Austria, September 2003.
Keywords: Glucose Intolerance, Myocardial Infarction, Life Style, Body Mass Index, Diabetes Mellitus, Type 2, Risk Factors, Hypoglycemic Agents, Confidence Intervals, Acarbose, Gastrointestinal Tract, Hypertension
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