Feb. 6 (Bloomberg) -- A U.S. government study was partially halted after researchers found an increase in deaths among type 2 diabetics who aggressively tried to keep their blood sugar levels normal.

Investigators stopped research 18 months early that compared standard blood-sugar control with an intense approach that included use of insulin, GlaxoSmithKline Plc's Avandia, Takeda Pharmaceutical Co.'s Actos, Eli Lilly & Co.'s Byetta, Bayer AG's Precose and generic medications.

Doctors have long thought that diabetics who aggressively reduced blood sugar to the levels recorded in healthy people would live longer and have fewer complications like heart attacks. Diabetes drugs are approved in the U.S. based on their ability to lower blood sugar.

``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,'' said Elizabeth Nabel, director of the National Heart Lung and Blood Institute. ``Less stringent'' goals may be best for these patients, she said.

More than 90 percent of U.S. diabetics have type 2, which often begins in adults and is linked to obesity. In that form, the body doesn't properly use insulin to convert blood sugar to energy, leading to a buildup in the heart, kidneys and other organs. In type 1 diabetes, which typically develops in childhood, the body doesn't produce insulin. The results of the study don't apply to those patients.

Avandia

The researchers were particularly interested in Glaxo's Avandia, since a review of studies involving the drug last year found it could boost heart attacks by more than 40 percent. The new report found that Avandia posed no additional risk, said William T. Friedewald, the chairman of the trial's steering committee and professor of public health at Columbia University.

``With our analysis so far, we've not been able to find any medication or combination of medications responsible for the increased risks,'' he said in a conference call. The risk also didn't stem from episodes of extremely low blood sugar, the researchers said.

The study, dubbed Accord, involved 10,251 diabetics with heart disease, high blood pressure, obesity or other high-risk conditions. Over two to seven years, 257 patients in the intensive treatment group and 203 in the standard group died. That translates to three additional deaths each year for every 1,000 patients, the researchers said.

State-Of-The-Art

Patients in the trial, who were also getting state-of-the- art medical care, had lower overall death rates than usual in such high-risk patients. Previous studies found about 4 percent to 6 percent of those patients die each year. The results indicate that there were about 10 percent fewer non-fatal heart attacks and strokes.

``If a heart attack did occur, it was more likely to be fatal,'' Friedewald said. ``We also had more unexpected sudden deaths without a heart attack.''

More than 20 million Americans have diabetes, and 234,000 die from it annually. Heart disease is the leading cause of mortality in patients with the disease, accounting for 65 percent of the deaths.

Most diabetics aren't now treated with the aggressively low blood sugar levels used in the study, said Judith Fradkin, director of the Diabetes, Endocrinology and Metabolic Diseases at the National Institute of Diabetes and Digestive and Kidney Diseases. As a result, it won't change their care, she said.

``People with diabetes should never adjust their treatment plan or goals without consulting their health care providers,'' she said in a statement.

Getting to Goal

Patients assigned to the aggressive control group struggled to reach hemoglobin A1C levels of less than 6 percent on blood- sugar tests. Only half the patients hit 6.4 percent or less, even with urging of their doctors and a barrage of daily drugs and tests, said John Buse, president of the American Diabetes Association and chief of endocrinology at the University of North Carolina at Chapel Hill.

``This raises as many questions as it answers,'' said Steven Nissen, head of cardiology at the Cleveland Clinic whose study first raised questions about Avandia. ``To lower hemoglobin A1c to levels that are close to normal actually had the opposite of the intended effect. It does shake things up.''

Guidelines from the American Association of Clinical Endocrinologists target an A1c level of 6.5 percent. The American Diabetes Association's goal is below 7 percent.

Maintain Good Control

Patients who were getting the intensive blood-sugar control will now be prescribed a less aggressive drug regimen, the researchers said. Those patients were also participating in another portion of the study that compares control of high blood pressure and cholesterol levels. That work will continue until the planned end of the study in June 2009.

In a statement on the Accord trial findings, the American Diabetes Association advised patients to maintain good control of blood sugar and to talk to their doctors. Previous studies showed tight blood sugar control reduces heart risk in patients with type 1 diabetes and kidney and eye damage in those with type 2 disease, the group said.

``The importance of glucose control in diabetes is firmly established,'' the ADA said. The guidelines state ``treatment should be tailored to the individual patient and that for some people with diabetes, intensive glucose control may not be warranted,'' particularly in middle-aged and older adults with a long history of diabetes and heart disease, they said.

Another Study

Another, smaller study published today in the New England Journal of Medicine found that intensive diabetes therapies, blood-pressure treatments and aspirin cut the death rate of diabetes patients compared with those getting standard therapy.

The study, conducted by Dr. Peter Goede at the Steno Diabetes Center in Copenhagen and colleagues, followed 160 patients with type 2 diabetes and microalbuminuria, an early indicator of chronic kidney disease in diabetic patients. The treatment lasted 7.8 years, followed by 5.5 years of observation.

In the intensive treatment group, 24 patients died, while 40 died in the standard therapy group. The intensive group had fewer heart complications, and only one patient progressed to end-stage renal disease, compared with six in the standard therapy group.

``Intensive intervention with multiple drug combinations and behavior modification appeared to have a sustained benefit in reducing vascular complications and death from any cause and from cardiovascular causes,'' the authors wrote.

The study didn't investigate if any single factor could have played a bigger role than others in preventing death.

To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net

Last Updated: February 6, 2008 18:17 EST