The belief that the lower the glucose level the better in patients with type 2 diabetes who are at a high risk for MI or stroke has been called into question by an ongoing NIH-supported trial. Aggressive reductions were found to be associated with an increased risk of death among such patients.
The trial began in 2001 and is scheduled to end in June 2009. It involves 10,251 patients (average age 62 years) who had type 2 diabetes for an average of 10 years. At baseline, the participants had hemoglobin A1c (HbA1c) levels of approximately 8.2%—higher than most type 2 patients. The subjects had, in addition to diabetes, known heart disease or at least two cardiovascular risk factors including hypertension, high cholesterol, obesity, and a smoking habit.
The patients were randomized to either the intensive medical treatment regimen to lower HbA1c levels to <6%, or a standard medical treatment regimen to lower levels to 7%-7.9%. After four years, the intensive-treatment group achieved a median HbA1c level of 6.4% and the standard group, 7.5%. But in the intensive-treatment group, 257 patients died (14 deaths per 1,000 patients), whereas 203 died (11 deaths per 1,000) in the standard-care group. This led the National Heart, Lung, and Blood Institute (NHLBI) to halt the intensive-treatment regimen and switch the patients to standard care. (Patients will continue to participate in other parts of the study examining the effects of treatments for BP or blood lipids.)
“A review of the data shows that if you have type 2 diabetes and are at especially high risk for heart disease, very intensive glucose-lowering treatments aimed at normalizing blood glucose to an HbA1c of less than 6% may be detrimental,” said NHLBI director Elizabeth Nabel, MD. On the whole, however, the death rates in both treatment groups were lower than those seen in similar populations, she added.
The American Diabetes Association recommends an HbA1c goal of <7% for most people with diabetes, citing “great benefit” at that level. And it says another trial involving 11,140 patients that has been under way for five years is showing that intensive control comparable to that in the NIH trial does not increase mortality. More definitive results will be available soon.