Rosiglitazone not linked with increased mortality

A nearly 7-year study of the effect of intensive blood sugar control with rosiglitazone (Avandia, GlaxoSmithKline) on the progression of cardiovascular disease in type 2 diabetes showed a slight reduction in cardiovascular events and no increase in mortality, in contrast to the results of a similar trial earlier this year.

The results of the Veterans Affairs Diabetes Trial were announced here during the 68th Annual Scientific Sessions of the American Diabetes Association by Dr. William C. Duckworth of the University of Arizona and the VA Medical Center in Phoenix and co-investigators in the study.

The Veterans Affairs Diabetes Trial, along with ADVANCE and ACCORD, were headliners at this year’s Sessions, evaluating the link between intensive glucose control and progression of CVD.

The 10,251-patient Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was halted prematurely in February when it appeared that tight glucose control increased the risk of heart attacks and showed a trend toward an increase in cardiovascular deaths.

Other ACCORD findings reported here showed that intensive treatment was no more effective than standard therapy in reducing cardiovascular events and it was associated with a high incidence of low blood sugar (hypoglycemia) and weight gain.

In the Veterans Affairs Diabetes Trial, 1791 patients (97 percent men) with poorly controlled type 2 diabetes were randomly assigned to intensive therapy with rosiglitazone, with target hemoglobin A1C levels below 7.0 percent; or to standard glucose control therapy aimed at achieving hemoglobin A1C levels between 8.0 percent and 9.0 percent. The average A1C level at the beginning of the study was 9.4 percent

The patients were followed for an average of 6.5 years. “We just closed the trial a little more than a week ago, on May 30, so the data are brand new,” said statistician Thomas E. Moritz, MS, of the Hines VA Hospital in Illinois.

He said that a rough analysis indicates that there appeared to be no adverse cardiovascular effects with the drug. “If anything, rosiglitazone showed a protective effect” against cardiovascular disease.

Duckworth also emphasized there was “no effect” on cardiovascular events with intensive glycemic control. “We didn’t even come near the predicted number of cardiovascular events and deaths.”

“The number one predictor of a cardiovascular event was hypoglycemia, specifically recent, severe episodes,” Duckworth reported. The investigators defined severe as an episode causing an alteration in mental status or loss of consciousness and recent as within 3 months of the event.

Among other VA study findings:

* Blood pressure dropped from 131/77 mm Hg at study entry to 127/70 mm Hg within 6 months and remained lower throughout the trial;

* LDL cholesterol dropped from 106 mg/dL at study entry to 78 mg/dL by year 5; HDL increased from 34 mg/dL at study entry to 39 mg/dL and 40 mg/dL in the standard and intensive groups, respectively; and triglycerides dropped from 157 mg/dL to 135 mg/dL in the standard group and to 128 mg/dL in the intensive group;

* Hemoglobin A1C levels averaged 6.9 percent with intensive glycemic control and 8.4 percent with standard therapy.

“From the time of first diagnosis of type 2 diabetes, the benefits of intensive glycemic control slowly decrease,” Duckworth commented to Reuters Health after his presentation. “Early on, there are strong benefits. Later, there may be detrimental effects with intensive glycemic control.” So what everyone thought was benign - hypoglycemia—is not.

Summing up, he said: “The findings clarify what is important—early intensive therapy, with careful monitoring to prevent hypoglycemia.”

A release issued by GlaxoSmithKline—prior to the announcement of the Veterans Affairs Diabetes Trial findings—with the headline “Important Cardiovascular Safety News on Avandia,” was immediately disowned by the American Diabetes Association and the Veterans Affairs Diabetes Trial researchers, who asserted that they had not released any data to the company.

SAN FRANCISCO (Reuters Health)