The first major head-to-head study comparing the newer diabetes drug Avandia with the older medicines metformin and glyburide shows that Avandia provides better glucose control than metformin, but carries more serious side effects and a higher cost, researchers said Monday.
"Metformin is still the first drug of choice" for newly diagnosed Type 2 diabetics, said Dr. Steven E. Kahn of the University of Washington and the Veterans Affairs Puget Sound Health Care System, who led the study.
Avandia, whose generic name is rosiglitazone, and metformin performed substantially better than glyburide, however.
"People who use glyburide will have to think about changing drugs," Kahn said. "In my opinion, the use of glyburide for any reason other than cost is going to become harder to justify."
Glyburide, a generic sold under the brand names Micronase and Diabeta, among others, is the least costly of the three drugs. It is used by some physicians in this country as first-line therapy but is more widely used overseas.
The study was funded by Avandia's manufacturer, GlaxoSmithKline. Kahn reported receiving consulting payments, grants and lecture fees from the company.
The results of the study were reported Monday at the 19th World Diabetes Congress in Cape Town, South Africa, and will be published Thursday in the New England Journal of Medicine.
The study enrolled 4,360 newly diagnosed diabetics who had never received drug therapy for the disorder. The patients were randomly divided into three groups, each of which received one of the drugs. The main goal of the study was to determine the time until the therapy stopped working and the patients required a second drug for glucose control.
At the end of five years, 15% of patients receiving Avandia needed a second drug, compared with 21% of those receiving metformin and 32% of those receiving glyburide.
But 62 of the patients taking Avandia developed a heart problem, compared with 58 taking metformin and 41 taking glyburide. A previous study had also shown an apparent increase in heart problems among Avandia users.
Avandia users retained more water than those taking the other drugs. They were also twice as likely to suffer bone fractures in the hands and feet, a problem more pronounced in women. Those taking Avandia gained 10 pounds over five years compared with a gain of three pounds on glyburide and a loss of six on metformin.
The study design defined failure of a drug to occur when fasting blood glucose levels rose above 180 milligrams per deciliter, the standard that was in use when the study was organized.
More recently, physicians have begun to rely on a different measurement, called glycated hemoglobin, a cumulative measure of blood sugar over two to three months.
By this test, the difference between Avandia and metformin -- a generic also sold under the brand names Glucophage and Fortamet, among others -- was smaller, wrote Dr. David M. Nathan of Massachusetts General Hospital in an editorial accompanying the report in the medical journal.
Given the "modest" benefit of Avandia, he wrote, "metformin remains the logical choice when initiating pharmacotherapy for Type 2 diabetes.
Nathan reported receiving financial support from GlaxoSmithKline for an educational program and grant support from competing companies.