Unexpected number of deaths halts part of diabetes study

TORONTO—Organizers of a large clinical trial aimed at reducing the heart disease risk of people with Type 2 diabetes announced yesterday they ended one arm of the study early after seeing an unexpectedly higher rate of deaths in people being aggressively treated for their diabetes.
The study, financed and conducted by the U.S. Heart, Lung and Blood Institute, found more deaths among people randomly assigned to the arm aiming to drive blood sugar counts down to pre-diabetes levels compared to those whose goal was standard blood sugar control.

While the death rates in both groups were lower than in people with long-term Type 2 diabetes in the general population, the researchers, on the advice of the experts on their data safety monitoring board, decided they couldn’t continue to put the people in the aggressive treatment arm at what seemed to be a greater risk.
“A thorough review of the data shows that the medical treatment strategy of intensively reducing blood sugar below current clinical guidelines causes harm in these especially high-risk patients with Type 2 diabetes,” Dr. Elizabeth Nabel, director of the institute, said in announcing the early stop to this part of the trial.
The researchers said the message for people with Type 2 diabetes and their health-care providers is that it is advisable to aim for moderate diabetes control in people who have been diabetics for a number of years and who already have risk factors for heart disease.
“Right now, my advice would be that in patients who are at high cardiovascular risk and—very importantly—and whose glucose levels are poorly-controlled right now that we should be targeting usual or good but not perfect A1C levels until we know more,’’ said Dr. Hertzel Gerstein, a diabetes expert from McMaster University in Hamilton, who led the blood sugar reduction arm of the study.
A1C is the test used to gauge blood glucose levels.
“I think that would be the safe advice and an important one for people to hear,” Gerstein, who also was the principal investigator for the Canadian study sites, said in an interview from Washington.
The study, which began in 2001, enrolled 10,251 people from the United States and Canada who were diagnosed with diabetes and were at high risk of heart disease.
The study, which included 1,500 people in Canada, was designed to determine whether intensive lowering of blood sugar levels, intensive lowering of blood pressure, or treatment of blood lipids (fats) with a triglyceride-lowering drug called a fibrate plus a statin drug could reduce the risk of major cardiovascular disease events in Type 2 diabetics at especially high-risk of having them.
Only the blood sugar levels portion of the research was ended early. The remaining arms of the study will continue until June, 2009 as planned.
In a teleconference for journalists, the researchers admitted the findings were puzzling and disappointing.
They said they had not yet found a way to explain why deaths were higher in patients receiving the aggressive blood sugar-lowering therapy, though they said analysis does not implicate a once-popular diabetes control drug, Avandia (rosiglitizone), which recent studies have suggested raises the risk of heart attacks and deaths in people who take it.
There were 257 deaths in the aggressive treatment group versus 203 in the group of patients whose care was aimed at getting blood sugar levels to current U.S. standard goals of between 7.0 and 7.9 percent.
Those in the aggressive care arm were aiming to get their blood sugar levels down under 6.0—in other words, down to the levels of people who do not have Type 2 diabetes.
People in both groups received all major classes of drugs approved to treat diabetes, but the number and dosages of these drugs varied, depending on individual need and what their blood sugar goal was.