SAN FRANCISCO — It's okay to push for a rapid drop in high hemoglobin A1c levels and tight glycemic control in patients with diabetes, but it's probably smart to ease up if there's no response within a year.
That's the key message from the recent major trials of aggressive glycemic control, Dr. Richard M. Bergenstal said at a meeting sponsored by the American Diabetes Association.
Many patients—but not all—can get their HbA1c level below 7% and help prevent microvascular disease, if that's a goal the patient embraces and the physician provides the right therapies.
“Push hard, work with a team, make good choices, and if there's no response, be careful. Don't keep pushing, pushing, pushing,” said Dr. Bergenstal, president of medicine and science for the ADA and executive director of the International Diabetes Center in Saint Louis Park, Minn.
HbA1c levels plummeted in the first year of intensive treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (N. Engl. J. Med. 2008;358:2545–59) but decreased more gradually in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial (N. Engl. J. Med. 2008;358:2560–72).
Contrary to what many have presumed, however, the increased risk of death in ACCORD in the intensive-therapy group compared with the standard-therapy group was not associated with fast decrease in HbA1c, he said.
In a yet-to-be-published analysis, there was no increased mortality in ACCORD patients whose HbA1c declined in the first year, and there was increased mortality if the HbA1c did not drop. “It's just the opposite of what you might think. If you drop rapidly, you do fine. If you don't drop, you are at risk of dying,” probably because “there's something going on in your life or in your physiology” that increases risk, Dr. Bergenstal said.
Pushing hard to get the HbA1c level below 6% may be overkill if the patient is not responding, he added.
This was the goal of intensive therapy in the ACCORD trial, which was associated with increased cardiovascular risk. The unpublished analysis, however, showed that patients on intensive therapy who achieved lower HbA1c levels were less likely to die.
“So, yes, the ACCORD intensive group had higher mortality” compared with the standard-therapy group “but it was people who could not get to goal,” Dr. Bergenstal explained. “If you are working hard, hard, hard and not getting a response, that is the person you back off on. They're not going to get to goal, and you're probably going to cause more harm than benefit.” This shouldn't be an excuse for not trying to get HbA1c down initially, however, at least to less than 7%, he added.
Lessons to be learned from these studies and the other recent major trial of tight glucose control, the Veterans Affairs Diabetes Trial (VADT), go far beyond management of HbA1c, Dr. Bergenstal said. “I think relying on the A1c alone is causing part of the problem” in getting too few patients to glycemic goals, he said.
Organizing a clinical practice for success is a team effort that should include a nurse, educator, and/or pharmacist who can help monitor patients between physician visits and initiate a change in therapy according to an agreed-upon algorithm that serves as a checklist, not a cookbook, he suggested. A team helps motivate patient lifestyle changes and helps patients cope with pain or depression.
It's very important that patients and physicians agree on the goals of therapy, and that the right therapies are chosen to meet those goals, he added. Some patients, for example, may be more afraid of increasing their risk for hypoglycemic episodes with intensive therapy than of the risk for complications from higher HbA1c levels. Others may be more concerned about avoiding the weight gain associated with some medications than about lowering HbA1c levels.
Disclosures for both stories: Dr. Bergenstal has held stock in Merck & Co. and participated in research or been a consultant for that company as well as Abbott Diabetes Care, Amylin Pharmaceuticals, Bayer, Eli Lilly and Co., Intuity Medical, LifeScan (Johnson & Johnson), Mannkind Corp., Medtronic, Novo Nordisk, ResMed, Roche Diagnostics Corp., Sanofi-Aventis, Pfizer, and Takeda Pharmaceuticals.