A drug that controls blood pressure and reduces heart risk also appears to protect against diabetes, especially in high-risk people, according to new research presented at the American Society of Hypertension's Twentieth Annual Scientific Meeting and Exposition (ASH 2005) by a University of Michigan physician who helped lead the study.
In new results from the VALUE trial that pitted the drug valsartan against another blood pressure drug, amlodipine, the patients taking valsartan were found to have a 23 percent lower risk of developing diabetes during the four or more years of the study. The two drugs had previously been shown to be roughly equivalent in reducing the risk of heart attack and stroke.
The new in-depth analysis of data from the two groups of patients shows that the difference in diabetes onset risk appears to be attributable to valsartan, and not to other underlying factors. But the researchers did determine that certain risk factors made certain patients more likely to develop diabetes -- and that the more of these risk factors a patient had, the more protective the effect of valsartan.
The randomized trial involved 15,313 patients at 942 sites in 31 countries, of whom 9,995 did not have diabetes at the start of the study. All patients were over age 50 and had high blood pressure and were at high risk for having a cardiac event. By the end of four or more years of follow-up, 11.5 percent of the patients taking valsartan had developed diabetes, compared with 14.5 percent of patients taking amlodipine.
"These new results should help physicians as they select anti-hypertensive agents for their patients, especially for those at higher risk of developing diabetes," says Ken Jamerson, M.D., the U-M professor of internal medicine who presented the results in a late-breaking session and served as VALUE chair for the United States. "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."
High blood sugar, faster heart rate, high body mass index, the concurrent use of a diuretic drug and beta blocker drug, non-white race and younger age were all associated with a higher risk of developing diabetes in all VALUE participants. But after all these variables were taken into account, patients who took valsartan had less of a chance of developing diabetes.
Valsartan is known commercially as Diovan, and is marketed by Novartis, which sponsored the VALUE trial. VALUE stands for Valsartan Antihypertensive Long-Term Use Evaluation. The trial was chaired by U-M emeritus professor of internal medicine Stevo Julius, M.D.
Julius and Jamerson, both members of the U-M Cardiovascular Center, both note that diabetes onset prevention was not a primary goal of the VALUE study, and that therefore more research is needed to confirm the finding. But they also point out that it's the first study in which a drug in the angiotensin II receptor blocker (ARB) class, valsartan, was pitted against a calcium-channel blocker (CCB) drug, amlodipine.
Until the VALUE trial, there had been no direct comparison of the two drugs in either cardiovascular events or new onset of diabetes.
"We know many factors increase the risk of diabetes, but valsartan appears to be important in that it provides protection against diabetes," says Jamerson. "Many patients with hypertension are also obese and have other risk factors that predispose them to develop diabetes. This trial adds to the armamentarium that physicians can choose from when treating patients with high diabetes risk."
The researchers separated the VALUE trial participants who weren't diabetic at the start of the trial into three groups, depending on the number of diabetes-predicting factors they had. The patients in the highest-risk group were six times more likely than the lowest-risk group to develop diabetes during the trial period. But among the patients in the highest-risk and second-highest-risk groups, the patients taking valsartan were significantly less likely to develop diabetes.
This finding, the authors say, suggests valsartan has some effect on glucose metabolism -- a crucial factor in diabetes risk.
An estimated one in three Americans have hypertension, or high blood pressure, which is defined as any level higher than 140/90. (Blood pressure is considered high if the top number is 140 or over, the bottom number is 90 or over, or both.)
If uncontrolled for long periods of time, high blood pressure puts people at a much greater risk of heart attack, stroke and other cardiovascular problems. High blood pressure is especially common among African Americans, middle-aged and elderly people, people who are overweight, people with diabetes, heavy drinkers and women taking birth control pills.
A wide range of drugs is available to help control blood pressure, and diet and exercise have been shown to help as well. ARBs and CCBs, the two classes of drugs represented in the VALUE study, are newer and more expensive than older diuretics and beta blockers. But researchers are continuing to find, through studies such as VALUE, that certain drugs may hold more benefit for certain groups of patients than for others. The VALUE trial is the largest study involving an ARB ever performed.
Jamerson presented the results on behalf of the entire VALUE team; the new analysis was led by Sverre Kjeldsen, M.D., Ph.D., who has held an adjunct position at the U-M and is chief of cardiology at the Ullevaal University Hospital in Oslo, Norway.