Michael Farkouh, MD, MSc
In older adults with impaired glucose tolerance and known cardiovascular (CV) disease or risk factors, does nateglinide reduce risk for diabetes and CV events?
Randomized, 2×2 factorial, placebo-controlled trial (Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research [NAVIGATOR]). ClinicalTrials.gov NCT00097786.
Blinded (patients, clinicians, data collectors, outcome assessors, and outcome adjudication committee).*
Median 5 years for diabetes and 6 years for CV events.
806 centers in 40 countries.
9518 patients ≥ 50 years of age (mean age 64 y, 51% women) who had impaired glucose tolerance (plasma glucose level ≥ 7.8 mmol/L [140 mg/dL] and < 11.1 mmol/L [200 mg/dL] 2 h after a 75-g oral glucose load), fasting plasma glucose level ≥ 5.3 mmol/L (95 mg/dL) and < 7.0 mmol/L (126 mg/dL), and ≥ 1 CV risk factor (if ≥ 55 y) or known CV disease (if ≥ 50 y). Exclusion criteria included current use of an angiotensin-converting enzyme inhibitor or an angiotensin-receptor blocker for hypertension and use of antidiabetic medication in ≤ 5 years. 212 randomized patients were excluded from the analysis because of protocol deficiencies at 10 sites.
Nateglinide, 30 mg taken before meals 3 times/d, increased after 2 weeks to 60 mg (n = 4645), or placebo (n = 4661). Patients were also randomized to valsartan or placebo. All patients participated in a lifestyle-modification program.
Incidence of diabetes (fasting plasma glucose level ≥ 7.0 mmol/L or 2-h plasma glucose level ≥ 11.1 mmol/L), core CV composite outcome (death from CV causes, myocardial infarction, stroke, or hospitalization for heart failure), and extended CV composite outcome (core components plus arterial revascularization or hospitalization for unstable angina).
85% (intention-to-treat analysis).
Nateglinide did not reduce risk for diabetes or CV events (Table). Nateglinide did not differ from placebo for any of the CV components: death from CV causes (2.7% vs 2.5%), fatal or nonfatal myocardial infarction (2.9% vs 3.1%), fatal or nonfatal stroke (2.4% vs 2.7%), hospitalization for heart failure (1.8% vs 2.1%), hospitalization for unstable angina (4.8% vs 5.4%), or arterial revascularization (7.1% vs 6.8%).
In older adults with impaired glucose tolerance and known cardiovascular (CV) disease or risk factors, nateglinide did not prevent diabetes or reduce risk for CV events.
Nateglinide vs placebo to prevent diabetes and cardiovascular (CV) events in older adults with impaired glucose tolerance and CV disease or risk factors†
†Abbreviations defined in Glossary. RRI, RRR, NNH, NNT, and CI calculated from hazard ratios in article.
‡Death from CV causes, myocardial infarction, stroke, or hospitalization for heart failure.
§Core components plus arterial revascularization or hospitalization for unstable angina.
Farkouh M. Nateglinide did not reduce diabetes or CV events in patients with impaired glucose tolerance and CV risk factors. Ann Intern Med. ;152:JC6–10. doi: 10.7326/0003-4819-152-12-201006150-02010
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Published: Ann Intern Med. 2010;152(12):JC6-10.
Cardiology, Coronary Risk Factors, Diabetes, Endocrine and Metabolism, Prevention/Screening.
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