If you prefer your large, randomized clinical trial results to be clear, consistent, and readily clinically applicable, don’t look to (ACCORD).
The initial ACCORD (Action to Control Cardiovascular Risk in Diabetes) findings shocked everyone. One arm of the trial had to be stopped a year and a half early, in February 2008, because of an unexpected 22% increased risk of mortality among the patients with longstanding type 2 diabetes and risk factors for cardiovascular disease randomized to intensive treatment aiming for near-normal glucose control (hemoglobin A1c less than 6.0%). Experts are still struggling to explain why.
While ACCORD was the first trial to show increased mortality with intensive glycemic control, it was one of several to show lack of cardiovascular benefit. But some of those other trials still demonstrated a reduction in microvascular—eye, kidney, and nerve—complications with intensive glycemic control. Surely, ACCORD would at least fall in step there, no?
Um, not quite. Data presented at the annual Scientific Sessions of the American Diabetes Association and published simultaneously in the Lancet and the New England Journal of Medicine were unsatisfyingly mixed.
On the one hand, intensive control did reduce retinopathy progression, Dr. Emily Chew reported.
But at the time the intensive arm of ACCORD was stopped, there was no difference between groups in pre-specified combined endpoints of severe kidney disease, retinopathy, and neuropathy, Dr. Faramarz Ismail-Beigi reported. Certain individual endpoints, such as the development of microalbuminuria and cataract extraction, were improved with intensive control but others, like loss of vibratory sensation, showed no difference.
So what should the clinician do? At a press briefing, speakers tried to offer advice. Dr. Sue Kirkman of the ADA said intensively treating type 2 diabetes soon after diagnosis and before the development of complications may be beneficial, whereas attempting to aggressively treat once complications have developed may not help and might actually hurt. “It speaks to individualization,” she said.
Dr. Denise Simons-Morton added that one aspect of individualization is the concept of “patient-centered care,” in which the physician and patient determine treatment goals together. Some patients may be more willing to work on blood glucose control to prevent eye disease, whereas others may have concerns about doing that.
Dr. Hertzel C. Gerstein noted that although aiming for perfect blood sugar now appears to be inappropriate in patients similar to the ACCORD population, there is still evidence of benefit in aiming for the currently recommended targets of less than 7.0% or less than 6.5%.
“No clinical trial is going to tell you how to manage the person sitting across the table from you,” Dr. Gerstein said. Certainly not ACCORD, anyway.