Intensive blood sugar treatment in trial of diabetes and cardiovascular disease changed

The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health has stopped one treatment within a large, ongoing North American clinical trial of diabetes and cardiovascular disease 18 months early due to safety concerns after review of available data, although the study will continue.

In this trial of adults with type 2 diabetes at especially high risk for heart attack and stroke, the medical strategy to intensively lower blood glucose (sugar) below current recommendations increased the risk of death compared with a less-intensive standard treatment strategy. Study participants receiving intensive blood glucose lowering treatment will now receive the less-intensive standard treatment.

The ACCORD (Action to Control Cardiovascular Risk in Diabetes) study enrolled 10,251 participants. Of these, 257 in the intensive treatment group have died, compared with 203 within the standard treatment group. This is a difference of 54 deaths, or 3 per 1,000 participants each year, over an average of almost four years of treatment. The death rates in both groups were lower than seen in similar populations in other studies.

“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 G. Nabel, M.D., director, NHLBI. “Though we have stopped this part of the trial, we will continue to care for these participants, who now will receive the less-intensive standard treatment. In addition, we will continue to monitor the health of all participants, seek the underlying causes for this finding, and carry on with other important research within ACCORD.”

In stopping this part of the trial, Nabel accepted the recommendation of the 10-member Data and Safety Monitoring Board (DSMB) – an independent advisory group of experts in diabetes, cardiovascular disease, epidemiology, patient care, biostatistics, medical ethics, and clinical trial design that has been monitoring ACCORD since it began. A specific charge of any DSMB is to monitor participant safety.

ACCORD participants will continue to receive blood sugar treatment from their study clinicians until the planned trial conclusion in June 2009. Those participants in the intensive treatment group will now be treated to the same A1C goals as those already in the standard treatment group.

The intensive treatment group had a target blood sugar goal, measured by hemoglobin A1C, of less than 6 percent. This is similar to blood sugar levels in adults without diabetes. The standard treatment group aimed for a target similar to what is achieved, on average, by those with diabetes in the United States (A1C of 7 to 7.9 percent) and lower than at study entry.

“The ACCORD findings are important, but will not change therapy for most patients with type 2 diabetes. Few patients with high cardiovascular risk like those studied in ACCORD are treated to blood sugar levels as low as those tested in this study, “ said Judith Fradkin, M.D., director, Division of Diabetes, Endocrinology, and Metabolic Diseases at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). “People with diabetes should never adjust their treatment plan or goals without consulting their health care providers.”