Hertzel C. Gerstein, MD, MSc, FRCPC
Professor, McMaster University and Hamilton Health Sciences

Thank you, Bill. Before we go into more detail regarding the blood-sugar treatment approach in ACCORD, I'd like to take a few minutes to describe why we tested an intensive blood-sugar lowering approach.

Adults with type 2 diabetes are two to four times more likely to have a heart attack, stroke or to die from cardiovascular disease than people without diabetes. This likelihood is even higher if an individual with type 2 diabetes is middle aged or older, has had a heart attack or stroke in the past, and has other risk factors for cardiovascular disease. Other risk factors include high blood pressure, high cholesterol, being overweight or obese, or being a smoker.

A large body of research has shown that higher glucose levels predict a higher likelihood of fatal and nonfatal cardiovascular events. Other studies have shown that lowering blood sugar levels can significantly lower the risk of certain complications of diabetes such as eye, nerve, and kidney diseases. In addition, a major study in people with type 1 diabetes - which is a different form of diabetes and used to be called "juvenile" diabetes -- suggests that intensive blood-sugar lowering strategies reduce the risk of cardiovascular disease and death. Furthermore, a study in people with more recent onset of type 2 diabetes than ACCORD participants showed a trend toward fewer heart attacks. This body of research strongly suggests that lowering glucose levels to levels that are typically observed in people without diabetes could reduce the risk of cardiovascular disease in people with established type 2 diabetes.

But, until ACCORD, no major clinical trial had studied whether lowering a raised blood sugar level to a level similar to that seen in people without diabetes reduces the risk of cardiovascular disease in people with type 2 diabetes. In addition, no clinical trial has studied the effects of intensive blood sugar lowering in people with longstanding type 2 diabetes who already have cardiovascular disease or who have multiple risk factors for cardiovascular disease in addition to diabetes.

So, one of the key questions that ACCORD was designed to answer is whether intensively lowering blood sugar could reduce the risk of heart attack and stroke. Drs. Nabel and Friedewald have described the basic design of the study and the characteristics of the study participants.

The two blood-sugar lowering approaches studied by researchers in 77 centers in the United States and Canada used lifestyle approaches focused on modifying diet and physical activity, together with glucose-lowering drugs. All of the drugs were FDA-approved and are commonly used for glucose control in the general diabetes population. The choice of drugs was based on the doctor's medical judgment that took the clinical characteristics of the participant into consideration while maximizing safety and glucose-lowering effectiveness. Thus, the treatments used in ACCORD were similar to the way practicing physicians treat patients in the community.

Drugs representing all of the types of glucose-lowering therapies available when ACCORD began in 2001 were used, and a few more drugs were added as they became available. The same menu of medications were used in both treatment groups, although in different combinations and doses. The medications included metformin; thiazolidinediones, or TZD's (such as rosiglitazone, pioglitazone); injectable insulins; sulfonylureas (such as glimepiride, glipizide, glyburide, and gliclazide); acarbose, and exenatide. Although the same drugs were used by both treatment strategy groups, more drug combinations and higher doses were prescribed to participants assigned to the intensive glucose lowering group than the standard group, in order to reach their assigned A1C goal.

Participants in the intensive treatment group were seen approximately every 2 months at an ACCORD clinical center, and participants in the standard group were seen about every 4 months. At each visit, clinical staff reviewed the participant's health status, discussed with the participant any side effects of drugs, adjusted medication dosages as needed, tested the participant's blood sugar, and performed other measures as appropriate.

Volunteer participants in both groups also received most drugs free. They received state-of-the-art medical care, with access to diet and physical activity counseling, experts in diabetes care, and the latest information related to diabetes. They were also provided with free glucose monitoring equipment so they could check their own blood sugar levels and make adjustments at home to achieve the goals to which they had been assigned. It is our view that the high standard of care received by all participants contributed to the lower death rates in both groups compared to the rates in the general community.

On average, the volunteer participants in both treatment strategy groups achieved a stable level of glucose within 6 to 9 months after being enrolled. The average blood sugar levels for both groups were lower than when they entered the study. The intensive treatment group achieved on average lower A1C values than the standard treatment group participants. Half of the participants in the intensive group achieved an A1C of less than 6.4 percent. In the standard treatment group, half of the participants achieved an A1C of less than 7.5 percent. Both groups have maintained stable glucose control throughout the study, which to date is an average of about 4 years.

Now, I'd like to turn to Dr. Judy Fradkin from the NIH's National Institute of Diabetes and Digestive and Kidney Diseases.

Last updated: February 6, 2008