COMMENTARY

Diabetes in 2010: A1c, ACCORD, Avandia, Victoza, and More

Anne L. Peters, MD

Disclosures

December 29, 2010

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Hi. I'm Dr. Anne Peters, and today I'm going to discuss what happened in 2010 in the world of diabetes. The first headline is a negative headline. More and more and people are getting diabetes. It's estimated by the Centers for Disease Control and Prevention that in 2050, 1 in 3 Americans will have type 2 diabetes -- higher numbers than ever before. This is clearly a disease that's not going away and we're going to have to focus on it to deal with it effectively.

The next bit of news is that the A1c level, long used for treating diabetes, is finally officially part of the diagnostic criteria for diabetes. In January in the standards of care from the American Diabetes Association, the A1c took its place alongside fasting blood glucose level and oral glucose tolerance tests for the diagnosis of type 2 diabetes. This has engendered a fair amount of controversy, like all change does, but I personally like using the hemoglobin A1c for diagnosing diabetes. To a large extent, I've been doing it for many years. It's a very nice way to tell if somebody has sustained hyperglycemia. It's a measure that tells us what the blood glucose levels have been over the preceding 3 months, and it really helps us clinically determine where a patient fits on the spectrum and what kind of treatment they need. So, I'm very glad we can use the hemoglobin A1c level officially for diagnosing diabetes, and I believe it will be here to stay.

Another bit of news is from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. To refresh your memory, ACCORD was a big trial done in the United States and it involved 10,000 individuals, half of whom were randomly assigned to standard care with a target A1c of about 7.5%, and the other half were randomly assigned to a target A1c level of < 6%. This is a very low target. These patients were older, many already had a macrovascular disease event or were at high risk for a macrovascular disease event, had a longer duration of diabetes, and most of the patients in the intensively treated group ended up on insulin.

The ACCORD study was stopped early, after just 3 years because there was an increase in sudden death in the intensively treated patients. We are never going to know for certain why this happened, but it seems that it might have had something to do with severe hypoglycemia. The events of sudden death occurred mostly in patients who had struggled, who had A1c levels that were around 8% or 9% and weren't coming down after a year of intensive intervention to try to bring those A1c levels down. These were the patients who ended up having sudden death. So, it's unclear exactly what interplay occurred, but it is clear that we need to individualize our therapies and not take patients who are either at high risk for severe hypoglycemia or who aren't responding to what we're trying to do, and keep pushing them lower. In those patients, a higher target may well be acceptable.

The data that came out this year are new data about the risk for macrovascular disease. Looking at the ACCORD data (published in The New England Journal of Medicine), you can see a reduction in some of the factors involved in the progression and development of retinopathy, nephropathy, and neuropathy. So, they did show an improvement in microvascular disease in those intensively treated patients compared with those who were in the standard care group. Even though the ACCORD study didn't achieve its primary objective, which was to show that very tight glucose control lowered the risk for macrovascular events, it did support the evidence of which we are increasingly certain, which is that tight glucose control matters in terms of the risk for eye disease, kidney disease, and nerve damage.

That's the end of ACCORD, at least as far as I know. More data may be coming out. I also know that the American Diabetes Association guidelines and targets for care are not going to change based on ACCORD per se. The standards really do seem to hold up from the data that we obtained from ACCORD in terms of diabetic complications and their progression, but again I stress that it's very important to individualize treatment and that there is no "one size fits all" therapy for diabetes. In your older, more vulnerable patients who don't tolerate hypoglycemia, raise their targets. Don't try to push their A1c levels down too low. If you have a younger, healthy patient, in whom you can get the A1c level down as low as < 6% without hypoglycemia, then do it, because those patients also have potential benefit down the road.

Another trial that was reported, this one at the European Diabetes Meetings, was the Anglo-Danish-Dutch Study of Intensive Treatment In People With Screen Detected Diabetes in Primary Care (ADDITION) study. ADDITION was a study of 3000 individuals in the United Kingdom and Europe who basically were treated for their type 2 diabetes with standard practice. These patients were new onset, and had been screened for type 2 diabetes, diagnosed, and then put into the treatment algorithm. When investigators looked at the results between the patients who were intensively treated and those who received standard care, there weren't any big differences. This was a cardiovascular outcomes trial with all the interventions -- glucose, lipids, and blood pressure. Investigators really tried to get these patients' global risks reduced to show that this intensive intervention made a difference. Although the intensive intervention didn't seem to make a difference, the standard of care kept getting better throughout the trial, so the patients in the standard treatment group actually did better and better as well. In the end, the comparison was actually pretty weak. It did show, ironically, that good control of all patients, especially from the get-go, really does help improve their outcomes, but they didn't show a difference in the 2 arms.

There were a number of reports and reviews about diabetes and cancer in 2010. I think the key take-home message here is that patients with type 2 diabetes are at increased risk for cancer and that we need to make sure we do cancer screenings and take extra good care of those patients because they may be at greater risk.

In terms of the US Food and Drug Administration (FDA), the news was both good and bad in 2010. The good news was that the drug liraglutide (Victoza®) was approved. This is a GLP-1 agonist, it's a once-daily drug, and I find it extremely helpful in treating my patients with type 2 diabetes. The first GLP-1 agonist that came out was exenatide (Byetta®) about 5 years ago, and liraglutide was the second agent in this class. We had hoped that there would be a once-a-week Byetta approved, also a GLP-1 agonist, but this drug was slowed down in terms of its approval by the FDA. There were a number of other devices and techniques that were also slowed down in terms of their approval. For the most part this was not because of new data indicating something was wrong with the new drugs or devices, but rather that the FDA needed more data. The FDA has had a turnover in recent years, so that the people looking at these agents are asking for more data now before they will approve drugs and devices. A drug that has tangled a great deal with the FDA (Avandia®) -- there are new warnings on Avandia in terms of its use, and it's very restricted now. It's not going to be a first-line drug for the treatment of type 2 diabetes. Pioglitazone (Actos®), which is also a peroxisome proliferator-activated receptor-gamma agonist, is still on the market and the recommendations for its use haven't changed much.

My final note for 2010 is that a very old drug, metformin, which has been used worldwide since 1957, has only been shown to be better and better, which is a pretty good thing for a drug. We know the side effects associated with metformin, but recent data suggest that not only does this drug lower blood glucose levels, it also helps reduce rates of cancer in patients with type 2 diabetes and may also reduce mortality. Metformin holds up over the long haul and in all the treatment algorithms is really the first step in our pharmacologic treatment of patients with type 2 diabetes. So that's 2010. This has been Dr. Anne Peters for Medscape. Thank you.

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