Blood pressure drug reduces risk of new-onset diabetes

Cardiology Review® Online, July 2005, Volume 22, Issue 7


San Francisco—Primary results of the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial presented last year showed that treatment with the angiotensin receptor blocker (ARB) valsartan (Diovan) or the calcium channel blocker (CCB) amlodipine (Norvasc) had similar effects in patients with hypertension and a high risk of cardiac disease. For one of the other end points, however—new-onset diabetes—there was a 23% lower risk of developing diabetes in the valsartan group compared with the amlodipine group.

According to information presented at the 20th Annual Meeting of the American Society of Hypertension by Kenneth A. Jamerson, MD, professor of internal medicine at the University of Michigan (UM),

a new analysis of the diabetes end point in VALUE has reconfirmed the positive effect of valsartan on glucose metabolism. The new analysis of data showed that the difference in risk of diabetes onset appears to be attributable to valsartan and not to other underlying risk factors.

The original VALUE trial enrolled 15,313 patients in the United States and Europe, 9,995 of whom did not have diabetes at the start of the study. All patients were over age 50 and had hypertension and a high risk for having a cardiac event. At the end of 4 or more years of follow-up, 11.5% of patients taking valsartan had developed diabetes versus 14.5% of those taking amlodipine.

Commented Dr. Jamerson, “Since we know from other studies that other hypertension medications, such as diuretics, come with a higher risk of diabetes, this result is especially interesting.” His

UM colleague and VALUE trial chairman, Stevo Julius, MD, ScD, stated, “This analysis looked in great detail at which factors might predict new onset of diabetes in this population, and found that the difference in risk of onset must be due to an active effect of valsartan. Whether this is due to increased insulin sensitivity, prevention of oxidative stress, or some other mechanism is still to be determined.”

Prevention of new-onset diabetes was not a primary goal of the VALUE study, so more research will be needed to confirm these findings.

Patients with diabetes before randomization were excluded from the VALUE trial, and all cases of new-onset diabetes were identified according to three criteria: (1) reports in adverse events databases, (2) patient study forms showing a new diagnosis of diabetes or new use of antidiabetic medications, or (3) blood tests at the end of the study that showed serum glucose greater than 7.8 mmol/L.

Using this definition and a mean follow-up of 4.2 years, the patients in the highest-risk group were found to be six times more likely than those in the lowest-risk group

to develop diabetes, but those in the highest- and second-highest-risk groups who were taking valsartan were significantly less likely to develop diabetes. According to the authors, this suggests that valsartan has some effect on glucose metabolism beyond blood pressure lowering, but the mechanism remains unclear.

The implications and mechanisms

of valsartan in preventing new-onset

diabetes are currently being studied

in the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. The NAVIGATOR trial is attempting to determine if long-term administration of either drug will delay or reduce the development of type 2 diabetes and cardiovascular disease in patients with impaired glucose tolerance and at high cardiovascular risk.