Findings from three recent studies call into question diabetes treatment strategies promoting very tight glucose control for the prevention of complications.

Investigators for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial reported that aggressively lowering blood glucose in people with type 2 diabetes who are at particularly high risk for heart attack and stroke does not significantly reduce the risk of major cardiovascular (CV) events (N Engl J Med. 2008;358:2545-2559). (Medications were used to bring hemoglobin A1c [HbA1c] levels to <6% in this group; the American Diabetes Association recommends <7%.)

The intensive intervention was linked, however, with a previously unrecognized danger: Compared with type 2 diabetes patients receiving standard treatment to attain and maintain HbA1c levels of 7%-7.9%, the relative risk of death was 22% higher.

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The ACCORD results were published alongside those of the Action in Diabetes and Vascular Disease (ADVANCE) trial (N Engl J Med. 2008;358:2560-2572). This investigation of 11,140 people with type 2 diabetes yielded more expected outcomes: Intensive lowering of blood glucose (to an average HbA1c of 6.5%) significantly reduced the risk of serious vascular complications overall, primarily microvascular kidney disease. The intervention did not significantly lower the risk of major macrovascular events but appeared to provide at least some modest benefit.

A third study was released at the American Diabetes Association’s 68th Annual Scientific Sessions in San Francisco in June. The 7.5-year VA Diabetes Trial of Glycemic Control and Complications in Diabetes Mellitus Type 2 (VADT) included 1,791 patients, mostly male, approximately 60 years of age, with either established CV disease or multiple risk factors for it. Average HbA1c level upon entry was 9.5%, falling to 8.4% in the standard group and 6.9% in the intensive group within six months of treatment and maintained throughout the trial.

“While we did not find a significant benefit of glucose control on any of the individual components, all end points favor good glucose control except CV death, where there was a very slight, insignificant increase in the intensive group,” says William C. Duckworth, MD, professor of clinical medicine, University of Arizona College of Medicine in Tucson.