2 research outputs found
Effect of Nateglinide on the Incidence of Diabetes and Cardiovascular Events
BACKGROUND The ability of short-acting insulin secretagogues to reduce the risk of diabetes or cardiovascular events in people with impaired glucose tolerance is unknown. METHODS In a double-blind, randomized clinical trial, we assigned 9306 participants with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors to receive nateglinide (up to 60 mg three times daily) or placebo, in a 2-by-2 factorial design with valsartan or placebo, in addition to participation in a lifestyle modification program. We followed the participants for a median of 5.0 years for incident diabetes (and a median of 6.5 years for vital status). We evaluated the effect of nateglinide on the occurrence of three coprimary outcomes: the development of diabetes; a core cardiovascular outcome that was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure; and an extended cardiovascular outcome that was a composite of the individual components of the core composite cardiovascular outcome, hospitalization for unstable angina, or arterial revascularization. RESULTS After adjustment for multiple testing, nateglinide, as compared with placebo, did not significantly reduce the cumulative incidence of diabetes (36% and 34%, respectively; hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15; P = 0.05), the core composite cardiovascular outcome (7.9% and 8.3%, respectively; hazard ratio, 0.94, 95% CI, 0.82 to 1.09; P = 0.43), or the extended composite cardiovascular outcome (14.2% and 15.2%, respectively; hazard ratio, 0.93, 95% CI, 0.83 to 1.03; P = 0.16). Nateglinide did, however, increase the risk of hypoglycemia. CONCLUSIONS Among persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors, assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the coprimary composite cardiovascular outcomes. (ClinicalTrials.gov number, NCT00097786.
Effect of valsartan on the incidence of diabetes and cardiovascular events
Background
It is not known whether drugs that block the renin–angiotensin system reduce the risk
of diabetes and cardiovascular events in patients with impaired glucose tolerance.
Methods
In this double-blind, randomized clinical trial with a 2-by-2 factorial design, we
assigned 9306 patients with impaired glucose tolerance and established cardiovascular
disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily)
or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then
followed the patients for a median of 5.0 years for the development of diabetes (6.5
years for vital status). We studied the effects of valsartan on the occurrence of three
coprimary outcomes: the development of diabetes; an extended composite outcome
of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke,
hospitalization for heart failure, arterial revascularization, or hospitalization for
unstable angina; and a core composite outcome that excluded unstable angina and
revascularization.
Results
The cumulative incidence of diabetes was 33.1% in the valsartan group, as compared
with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86;
95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with
placebo, did not significantly reduce the incidence of either the extended cardiovascular
outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.43)
or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86
to 1.14; P=0.85).
Conclusions
Among patients with impaired glucose tolerance and cardiovascular disease or risk
factors, the use of valsartan for 5 years, along with lifestyle modification, led to a
relative reduction of 14% in the incidence of diabetes but did not reduce the rate of
cardiovascular events. (ClinicalTrials.gov number, NCT00097786.