Background: Several trials have reported that inhibiting the renin-angiotensin system (i.e., with angiotensin-converting enzyme [ACE] inhibitors or angiotensin receptor blockers [ARBs]) may prevent patients with hypertension or other cardiovascular disease from developing diabetes mellitus. However, this effect was not a primary outcome of most trials, and results were not confirmed by systematic glucose measurements. McMurray and colleagues used the NAVIGATOR (Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research) trial to study the effectiveness of ACE inhibitors and ARBs at reducing the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance.

The Study: Investigators randomized 9,306 patients to receive valsartan (Diovan) in dosages of 80 to 160 mg daily or placebo. All patients participated in a lifestyle intervention program designed to reduce the risk of diabetes. In addition to having impaired glucose tolerance, all eligible participants had preexisting cardiovascular disease or at least one risk factor for cardiovascular disease. Exclusion criteria included the use of antidiabetic medications within the previous five years, or the use of an ACE inhibitor or ARB for hypertension.

Three coprimary outcomes were evaluated: the incidence of diabetes; a composite cardiovascular outcome including development of heart failure, nonfatal myocardial infarction or stroke, unstable angina, arterial revascularization, or cardiovascular-associated death; and a similar composite cardiovascular outcome that excluded unstable angina and the need for revascularization.

Results: Diabetes was less likely to develop in the valsartan group than in the placebo group (33.1 versus 36.8 percent, respectively; hazard ratio = 0.86). Fasting and two-hour postload glucose levels were also lower in the valsartan group (−0.59 mg per dL [0.03 mmol per L] versus −3.15 mg per dL [0.17 mmol per L] in the placebo group). However, cardiovascular outcomes remained similar between the groups (14.5 versus 14.8 percent for placebo).

Conclusion: The authors conclude that valsartan therapy (in a dosage up to 160 mg daily) reduces the likelihood that patients with impaired glucose tolerance will develop diabetes (relative risk reduction = 14 percent). This translates into roughly 26 patients needing to be treated for five years to prevent one new case of diabetes. However, valsartan does not reduce the risk of cardiovascular events.