Large Diabetes Trial Halted After Deaths

A large diabetes study was interrupted yesterday because of an unexpected number of deaths. What's notable here is that only one arm of the study was halted, that involving participants who were undergoing aggressive blood glucose lowering strategies. The less intensive treatment arms are ongoing.

The study in question is the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which enlisted 10,251 patients with type 2 diabetes who were at high risk for heart disease. After about 4 years, there were 257 deaths in the intensive treatment arm and 203 deaths in those receiving standard BG treatment ... a difference of 54 deaths.

Elizabeth Nabel, director of the National Heart, Lung and Blood Institute (NHLBI) which is sponsoring the study, said, "The harm of the very intensive treatment outweighed the potential benefit."

Intensive Treatment

All participants received the same dietary and lifestyle recommendations. However, since the goal for those in the intensive treatment arm was to achieve an HbA1C < 6.0%, a fasting BG of 100 mg/dl or less, and a 2-hour postprandial BG of 140 mg/dl or less, several drug therapies were aggressively employed. The protocol stated:

"Most intensive group participants will likely be on 3 or more injections of insulin per day in addition to 2 or 3 oral agents." All patients in the intensive arm received a minimum of 2 oral agents.
- ACCORD Protocol, May 11, 2005

Those in the standard treatment groups used a combination of dietary, lifestyle and drug therapies to achieve an HbA1C of 7.0 to 7.9% and a fasting BG of 90 mg/dl or more. Postprandial BGs were not routinely used to guide therapy in this group, and healthcare contacts were less frequent and less intense.

ACCORD researchers have not yet determined the cause of the excessive deaths.

Dr. Steven Nissen, chairman of the department of cardiovascular medicine at the Cleveland Clinic speculated that patients may suffer unintended consequences from taking so many drugs, which might interact in unexpected ways.
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News summaries:
Deaths Halt Part of Diabetes Study, Scientists Fear Heart Attacks, Strokes Were Tied to Treatment, Washington Post
Diabetes Study Partially Halted After Deaths, New York Times

NHLBI press release:
For Safety, NHLBI Changes Intensive Blood Sugar Treatment Strategy in Clinical Trial of Diabetes and Cardiovascular Disease

ACCORD Trial online:
ACCORD