|New Type 2 Diabetes Drug Delays Disease Progression|
But side effects include cardiovascular risks, study finds
By Amanda Gardner
MONDAY, Dec. 4 (HealthDay News) -- One of a new class of diabetes drugs delayed the progression of type 2 diabetes along with the need to add additional medications.
But it's not clear how the findings will affect actual practice because diabetes drugs tend to involve a complicated constellation of benefits and side effects.
In particular, this drug, Avandia (rosiglitazone), resulted in blood sugar staying normal longer but carried with it various cardiovascular risks and is expensive.
"You have to take into consideration the potential benefit versus the potential risk," said Dr. Robert Rizza, past president of the American Diabetes Association and professor of medicine at the Mayo Clinic College of Medicine in Rochester, Minn.
The results of the trial are even less encouraging when taken in concert with a previous study that also found an excess of cardiovascular events.
"Because of the fact that adverse cardiovascular events went in the wrong direction in the [previous] trial and because they go in the wrong direction in this trial, I have concerns about the overall benefit of rosiglitazone in diabetic patients who are highly vulnerable to adverse cardiovascular outcomes, and this is not, in my view, a very favorable result," said Dr. Steven E. Nissen, interim chairman of the department of cardiovascular medicine at the Cleveland Clinic.
"Something is happening here which has pretty profound public health implications," added Nissen, who recently uncovered cardiac problems with muraglitazar, a not-yet-approved diabetes drug in the same class as Avandia, and published those findings in the Journal of the American Medical Association.
The new study appears in the Dec. 7 issue of the New England Journal of Medicine and is being released early to coincide with a presentation Monday at the World Diabetes Congress in Cape Town, South Africa.
More than 20 million people in the United States have type 2 diabetes, the most common form of the disease. People with this condition either don't produce enough insulin, or cells in the body don't utilize the hormone efficiently. Insulin is essential for transporting sugar from the blood to cells for energy. Keeping blood sugar levels normal or nearly normal is critical to reducing the risk of the long-term complications of diabetes such as heart disease, nerve damage, kidney damage, blindness and amputations.
According to an accompanying editorial in the journal, the approval of five new classes of anti-diabetes drugs in the past decade has left doctors unsure of which to use first or how to combine them with other drugs. In particular, it hasn't been clear how the class of drugs known as thiazolidenediones, which includes Avandia and muraglitazar, compare with other glucose-lowering medications. These drugs work by sensitizing muscle, liver and fat tissue to insulin.
This study compared 4,360 newly diagnosed type 2 diabetes patients receiving either Avandia (rosiglitazone, a thiazoidinedione made by GlaxoSmithKline); glyburide (Micronase); or metformin (Glucophage). Prior to the study, participants had not taken any medications for diabetes.
The trial was sponsored by Glaxo, and study lead author Dr. Steven Kahn disclosed having served as a consultant and speaker for the company.
Avandia delayed the need for additional drugs by 60 months, compared with 45 months for Glucophage and 33 months for Micronase.
Participants taking Avandia had more weight gain and edema while participants on Micronase had a lower risk of cardiovascular events. One unexpected finding was that women taking Avandia had more fractures, primarily in the hands and feet.
A surprisingly high proportion of participants dropped out of the study, the editorial pointed out.
And not only did Avandia have cardiovascular effects, it did so even though patients in this group were taking more of the cholesterol-lowering drugs known as statins because the drug appeared to raise their LDL ("bad") cholesterol, Nissen said.
Avandia seems clearly superior to Micronase, but the distinction between Avandia and Glucophage is less clear.
"In my opinion, the use of [Micronase] for any reason other than cost is going to become harder to justify," said Kahn, associate chief of staff for research at Veterans Affairs Puget Sound Health Care System and professor of medicine at the University of Washington, Seattle. "On the other hand, when you compare [Glucophage] and [Avandia], this is where it starts to become a little grayer... A lot more has to be done in terms of human investigation."
Overall, it's still not clear how physicians should treat patients.
"We're being inundated by medications, and we're being overwhelmed by patients who are not controlled by either one or even two medications. So, we're really talking about a condition that's going to be treated with multiple medications," said Dr. Stuart Weiss, clinical assistant professor of medicine at New York University School of Medicine. "The only thing that we can say is that combination therapy might be the best way to go from the beginning, and this study doesn't even address that."
For more about type 2 diabetes, visit the National Diabetes Information Clearinghouse.
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SOURCES: Steven E. Kahn, M.B., C.B., associate chief of staff, research, Veterans Affairs Puget Sound Health Care System, and professor, medicine, University of Washington, Seattle; Robert Rizza, M.D., past president, American Diabetes Association, and professor, medicine, Mayo Clinic College of Medicine, Rochester, Minn.; Steven E. Nissen, M.D., chairman, department of cardiovascular medicine, Cleveland Clinic, and president-elect, American College of Cardiology; Stuart Weiss, M.D., endocrinologist, New York University Medical Center and clinical assistant professor, NYU School of Medicine, New York City; Dec. 7, 2006, New England Journal of Medicine