16 March 2010

Search for Better Diabetes Therapy Falls Short

The Wall Street Journal
Current Treatments, While Effective, Failed to Also Help Prevent Heart Attacks and Stroke


ATLANTA—New strategies to prevent and treat diabetes and heart disease failed to improve care in two major studies, frustrating researchers' efforts to find more-effective approaches to the world's burgeoning diabetes epidemic.

The studies are among the first large trials to test whether treatments recommended for diabetes patients also reduce the risk of heart attacks and strokes. Diabetics are between two and four times as likely to die of cardiovascular causes as nondiabetics. The lack of data on whether strategies to treat diabetes actually lower heart risk is of growing concern to physicians, researchers and regulators.

One new study, called Accord, found that treating blood pressure to lower levels than recommended in current practice doesn't further reduce risk of death, heart attack and stroke among people with diabetes. The same study also found that the drug Tricor, marketed by Abbott Laboratories, failed to prevent such events even though it lowered levels of blood fats called triglycerides that are associated with high diabetes risk.

In the other report, dubbed Navigator, a diabetes drug called Starlix failed to prevent people at high risk of diabetes from progressing to the disease. The blood-pressure medicine Diovan did modestly reduce risk of developing diabetes in the same study, but neither drug significantly cut the risk of heart-related deaths, heart attacks and strokes. Both pills in this study are sold by Novartis SA of Switzerland.

The results from both studies were unveiled Sunday at the annual scientific meeting of the American College of Cardiology and published online in four different papers by the New England Journal of Medicine.

"Physicians and patients are looking pretty desperately to decrease the toll that comes with diabetes," said David Nathan, director of the diabetes center at Massachusetts General Hospital, Boston, who wasn't involved in the reports. "These studies don't provide a new route or any new information about how to do that."

More than 23 million Americans suffer from diabetes. The International Diabetes Federation, Brussels, puts the global total at 285 million, with projections that it will rise to 438 million within 20 years. The vast majority have Type 2 diabetes, an impaired ability to process dietary sugars that is typically associated with obesity and lack of exercise.


In the U.S., combined annual costs to treat the disease and for additional factors such as lost productivity amount to $174 billion, according to the American Heart Association. Heart experts worry that without better ways to prevent and treat diabetes, the disease threatens to reverse nearly a half-century of advances against cardiovascular disease, which remains the world's leading killer.

Despite the disappointing findings, researchers said that overall, the data strengthen support for current treatment guidelines and that patients shouldn't abandon proven medications and strategies that may be keeping them out of trouble.

"What we're seeing is the effectiveness of our current therapies," said Darren McGuire, a cardiologist and diabetes researcher at UT Southwestern Medical Center, Dallas. "It's not that what we're presently doing isn't good; it's just that more isn't better."

Researchers said the findings also underscore the value of physical exercise, healthy diets and weight loss. Even a loss of 5% of body weight, for instance, significantly lowers the risk of developing diabetes.

Among current guidelines for diabetes patients, one calls for treating systolic blood pressure–the higher number in a blood-pressure test–to below 130, though limited evidence exists for that recommendation. For patients with triglyceride levels above 200, advice is to try a so-called fenofibrate drug such as Tricor if a statin alone doesn't help, especially if HDL, or good cholesterol, is low. Evidence for that strategy isn't strong either.

In one part of the Accord trial involving 4,733 patients followed for 4.7 years, the group assigned to intensive treatment achieved systolic blood pressure averaging 119 (target: below 120), compared with 134 in the group getting standard care (target: below 140). Researchers said while the more intensive approach slightly lowered the likelihood of heart attack, stroke or death from cardiovascular causes, the difference wasn't statistically meaningful. A second Accord paper found that adding Tricor to a generic statin successfully reduced triglyceride levels by about 25%, but that didn't lead to fewer heart attacks, strokes and heart related deaths. Researchers said the results suggested women might do worse adding Tricor while men might do better.

In addition, the combination appeared to benefit a subgroup of patients with triglycerides above 204 and an HDL of 34 or lower, lending some support to current guidelines. But that finding didn't quite achieve statistical significance and would need confirmation in new trial.

Abbott said it wasn't surprised by the results because the average triglyceride level of patients when the study began was 162; it says most patients treated with its drug have levels over 200. Researchers said the study suggested adding Tricor to a statin might help some patients with high triglyceride levels. Tricor and a sister drug Triplipix together accounted for $1.3 billion in revenue for Abbott in 2009. The study was sponsored by the National Institutes of Health.

The Navigator study, sponsored by Novartis, examined whether Starlix or Diovan, when added to an exercise and diet program, would prevent diabetes and major cardiovascular events among high risk patients.

"For people who don't have diabetes, neither drug will be recommended," said Robert Califf, vice chancellor for clinical research, Duke University, Durham, N.C., and a leader of the trial, because neither achieved success against both diabetes and heart disease.

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