MedWire News: (7 February 2008) The US National Heart, Lung, and Blood Institute (NHLBI) has announced it is stopping the intensive glycemic control aspect of the ACCORD trial in Type 2 diabetes patients, owing to increased all-cause mortality among patients in the intensive compared with the standard glucose-lowering treatment arm.

"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," explained NHLBI director Elizabeth Nabel.

"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."

The ACCORD (Action to Control Cardiovascular Risk in Diabetes) study enrolled 10,251 participants with established Type 2 diabetes who were at high risk for cardiovascular disease due to having two or more other risk factors or a diagnosis of cardiovascular disease prior to enrollment. The trial was designed to compare three different approaches to reducing the high rate of cardiovascular events in these patients: intensive versus standard glucose-, BP-, and lipid-lowering treatments.

In the intensive glucose-lowering treatment arm, patients were treated with the aim of normalizing their glucose levels to a hemoglobin (Hb)A1c goal level of below 6%. The standard treatment aimed to get patients to the average HbA1c level currently achieved in clinical practice in diabetes patients in the USA of 7-7.9%.

The median HbA1c level achieved was 6.4% in the intensive-treatment and 7.5% in the standard-treatment group.

The ACCORD Data Safety Monitoring Board (DSMB) found that, after an average of 4 years of treatment, 257 participants in the intensive-treatment group had died compared with 203 in the standard-treatment group, translating into an excess of about three deaths per 1000 participants treated for a year and a 20% higher rate of death in the intensive versus standard group.

The data also revealed that the primary outcome of cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke was 10% lower in the intensive- versus standard-treatment groups, driven mainly by fewer nonfatal MIs. Nevertheless, the DSMB decided that the harm observed with the intensive treatment outweighed the potential benefit.

For both treatment groups, clinicians were free to choose from all major classes of antidiabetic medications currently available. So far, the ACCORD researchers have not determined a specific cause for the increased deaths with intensive treatment and found no evidence that any medication or combination is responsible.

ACCORD steering committee chair William Friedwald, from Columbia University in New York, USA, noted: "Because of the recent concerns with rosiglitazone, our extensive analysis included a specific review to determine whether there was any link between this particular medication and the increased deaths. We found no link."