Intensively targeting blood
sugar increases risk of death

Intensively targeting blood sugar to near-normal levels in adults with type 2 diabetes at especially high risk for heart attack and stroke does not significantly reduce the risk of major cardiovascular events, such as fatal or nonfatal heart attacks or stroke, but increases risk of death, compared to standard treatment. This is the main finding of the ACCORD (Action to Control Cardiovascular Risk in Diabetes) Control Cardiovascular Risk in Diabetes) clinical trial.

In the trial researchers compared a medical strategy aimed at near-normal blood sugar levels – below current recommendations – to a strategy to reach more standard blood sugar levels. The study evaluated the effects of intensively targeting blood sugar control among adults with established diabetes, high blood sugar levels, and preexisting heart disease or at least two cardiovascular disease risk factors in addition to diabetes.

The first published results of the ACCORD trial of over 10,000 participants appear in the New England Journal of Medicine (NEJM) on 12 June 2008.

In February, the US National Heart, Lung, and Blood Institute (NHLBI) stopped the intensive blood sugar strategy after an average of 3.5 years of treatment, instead of the planned 5.6 years, due to safety concerns. The intensive strategy group had a 22% higher risk of death – or 54 more deaths – compared to the standard group. The increased risk began emerging within 1 to 2 years after the strategy began to aggressively lower the participants' blood sugar levels. All participants now follow a medical strategy to reach the standard blood sugar levels while other components of the study continue.

“ACCORD is providing important evidence to help guide treatment recommendations for adults with established type 2 diabetes who have had a heart attack or stroke or who have two or more risk factors for cardiovascular disease in addition to diabetes,” said NHLBI Director Elizabeth G. Nabel, M.D. “For these individuals, intensively lowering blood sugar to near-normal levels appears to be too risky.”

“Despite detailed analyses, we have been unable to identify the precise cause of the increased risk of death in the intensive blood sugar strategy group,” noted lead author Hertzel C. Gerstein, MD, MSc. “Our analyses to date suggest that no specific medication or combination of medications is responsible. We believe that some unidentified combination of factors tied to the overall medical strategy is likely at play.” 

“The ACCORD results can now be considered when doctors are tailoring blood sugar strategies for adults with type 2 diabetes who are at especially high risk for cardiovascular disease,” said Denise G. Simons-Morton, MD, PhD, a coauthor and NHLBI project officer for ACCORD.

Therapy in both groups included patient education and counseling, and treatment with any of the major classes of Food and Drug Administration-approved diabetes medications, as prescribed by their study clinician: metformin, thiazolidinediones (TZDs, primarily rosiglitazone), insulins, sulfonylureas, exanatide, and acarbose. Combinations of medications could be used as needed to reach the treatment goals.

To meet their more aggressive targets, participants in the intensive group used more medications, were more likely to use combinations of medications, and changed medications and/or doses of medications more frequently than those in the standard group. For example, 52% of participants in the intensive strategy group were on three oral medications plus insulin compared with 16% of participants in the standard strategy group.

The intensive strategy was associated with more adverse side effects from medications, hypoglycemia (low blood sugar) events, weight gain, and fluid retention.

The researchers caution that the results might not apply to patients who are at lower risk of cardiovascular disease than the ACCORD participants or to patients with more recently diagnosed type 2 diabetes. On average, ACCORD participants had been diagnosed with diabetes for 10 years at enrollment.

ACCORD's ongoing studies of the effects of aggressively lowering blood pressure and treating multiple blood lipids (cholesterol and triglycerides) in high-risk diabetic patients are expected to continue through June 2009.

ate of upload: 16th November 2008

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