Glycemic Goals Clarified: HbA1c Of 7% Still Ceiling: Three groups issue position statement.

From: Clinical Endocrinology News

MIRIAM E. TUCKER (Senior Writer)

A target hemoglobin A1c of less than 7% should remain the general goal for nonpregnant adults with diabetes, despite the recent results from three large randomized trials showing that intensive glucose lowering did not reduce the risks of cardiovascular disease in people with longstanding type 2 diabetes.

But glycemic targets that are either more or less stringent than that standard may be prudent for certain individuals with diabetes, according to a joint position statement issued by the American College of Cardiology, American Diabetes Association, and American Heart Association and published online in their respective journals: the Journal of the American College of Cardiology, Diabetes Care, and Circulation.

“The ADA/AHA/ACC position statement is very well thought out and very well articulated. The authors should be commended for their concise analysis of the available data,” Dr. J. Michael Gonzalez-Campoy, medical director and CEO, Minnesota Center for Obesity, Metabolism, and Endocrinology, said in an interview.

The three organizations conducted a careful reexamination of glycemic control guidelines in light of the findings from the Action to Control Cardiovascular Risk in Diabetes (ACCORD), the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), and the Veterans Affairs Diabetes Trial (VADT). All showed no significant reduction in cardiovascular outcomes with intensive glucose control, but the ACCORD caused particular concern—and was halted early—because it showed a 22% increase in mortality among subjects randomized to a strategy of very intensive glycemic control with a target HbA1c of less than 6% (N. Engl. J. Med. 2008;358:2545–9).

Still, “The evidence obtained from ACCORD, ADVANCE, and VADT does not suggest the need for major changes in glycemic control targets, but rather additional clarification of the language that has consistently stressed individualization,” Dr. Jay S. Skyler and his associates wrote (Diabetes Care 2009;32:187–92).

Those clarifications include:
▸ To prevent microvascular and neuropathic complications in people with both type 1 and type 2 diabetes, the HbA1c goal for nonpregnant adults in general remains less than 7%. This recommendation is based on robust data from long-term studies including the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS).
The American Association of Clinical Endocrinologists (AACE), which was not part of the group issuing the statement, recommends aiming for an HbA1c level of 6.5% or less.
▸ The general HbA1c goal of less than 7% also “appears reasonable” for prevention of macrovascular disease among those with recent onset of diabetes, based on long-term follow-up of the DCCT and UKPDS cohorts.
▸ For selected individual patients, even lower HbA1c goals than the general goal of less than 7% might be reasonable, provided that this target can be achieved without significant hypoglycemia or other adverse effects of treatment. Such individuals might include those with short duration of diabetes, long life expectancy, and no significant cardiovascular disease. This recommendation was based on subgroup analyses of the DCCT, UKPDS, and the microvascular evidence from the ADVANCE trial.
▸ Conversely, less stringent HbA1c goals may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, or extensive comorbid conditions or those with longstanding diabetes in whom the general goal is difficult to attain despite diabetes self-management and education, appropriate glucose monitoring, and effective doses of multiple glucose-lowering agents, including insulin.
▸ For primary and secondary cardiovascular risk reduction in patients with diabetes, providers should continue to follow the evidence-based recommendations for blood pressure treatment, lipid-lowering with statins, aspirin prophylaxis, smoking cessation, and healthy lifestyle behaviors delineated in the ADA Standards of Medical Care in Diabetes (Diabetes Care 2008;31[suppl 1]:s12–54) and the AHA/ADA guidelines for primary CVD prevention (Circulation 2007;115?:114–26).

Dr. Gonzalez-Campoy, who serves on the AACE board of directors, agreed with the recommendations. “The ACCORD, ADVANCE, and VADT emphasize the need to individualize care. … The recent publications that show no benefit in cardiovascular outcomes with attempts at normalizing glycemic control were all done on people with [longstanding] type 2 diabetes. Therefore, these findings are not applicable to people with type 1 diabetes, nor do they apply to people with new-onset diabetes mellitus.”

“People with type 2 diabetes who may achieve normal A1c values with lifestyle changes alone, or with weight management, should not increase their A1c values,” Dr. Gonzalez-Campoy added.
Indeed, a substudy of VADT presented at the ADA's annual meeting in June suggested that individuals earlier in their history of type 2 diabetes had the most benefit of improved glycemic control, noted Dr. Daniel Einhorn, head of the Sharp Diabetes Treatment and Research Center, San Diego.

“The key is not to throw out the baby with the bathwater. The VADT and ACCORD suggest that some populations may not benefit from tight glycemic control and there may be risks associated with tight control in these same populations, i.e with cardiovascular disease and/or increased risk of hypoglycemia. This does not detract from the wealth of information that good glycemic control confers benefit on microvascular disease and, given a long enough window, cardiovascular disease,” said Dr. Einhorn, also on the AACE board of directors.

Dr. Einhorn is a consultant to Takeda, Eli Lilly, Amylin Pharmaceuticals, and Merck.