Effect of Nateglinide on the Incidence of Diabetes and Cardiovascular Events

Holman, R. R. et al. (2010) Effect of Nateglinide on the Incidence of Diabetes and Cardiovascular Events. New England Journal of Medicine, 362(16), pp. 1463-1476. (doi:10.1056/NEJMoa1001122)

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Abstract

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.)

Item Type:Articles
Keywords:10-YEAR FOLLOW-UP cardiovascular disease CARDIOVASCULAR EVENTS cardiovascular risk CARDIOVASCULAR-DISEASE CARE Classification DEATH DESIGN diabetes DISEASE DOUBLE-BLIND ENGLAND EVENTS FAILURE FASTING GLUCOSE GLUCOSE GLUCOSE-TOLERANCE HEART Heart failure HEART-FAILURE Impaired glucose tolerance IMPAIRED GLUCOSE-TOLERANCE Incidence INCREASE INFARCTION insulin INTERVAL LIFE-STYLE MELLITUS Metabolism Myocardial infarction MYOCARDIAL-INFARCTION Nateglinide NIDDM NUMBER outcome OUTCOMES PEOPLE PHASE INSULIN-SECRETION PREVENTION PROGRAM RANDOMIZED CONTROLLED-TRIAL RISK risk factors RISK-FACTOR RISK-FACTORS stroke TRIAL trials UNSTABLE ANGINA Valsartan
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McMurray, Professor John
Authors: Holman, R. R., Haffner, S. M., McMurray, J. J., Bethel, M. A., Holzhauer, B., Hua, T. A., Belenkov, Y., Boolell, M., Buse, J. B., Buckley, B. M., Chacra, A. R., Chiang, F. T., Charbonnel, B., Chow, C. C., Davies, M. J., Deedwania, P., Diem, P., Einhorn, D., Fonseca, V., Fulcher, G. R., Gaciong, Z., Gaztambide, S., Giles, T., Horton, E., Ilkova, H., Jenssen, T., Kahn, S. E., Krum, H., Laakso, M., Leiter, L. A., Levitt, N. S., Mareev, V., Martinez, F., Masson, C., Mazzone, T., Meaney, E., Nesto, R., Pan, C. Y., Prager, R., Raptis, S. A., Rutten, G. E. H. M., Sandstroem, H., Schaper, F., Scheen, A., Schmitz, O., Sinay, I., Soska, V., Stender, S., Tamas, G., Tognoni, G., Tuomilehto, J., Villamil, A. S., Vozar, J., and Califf, R. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences
Journal Name:New England Journal of Medicine
Publisher:Massachusetts Medical Society
ISSN:0028-4793
ISSN (Online):1533-4406

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