More Questions Than Answers

(Justin Sullivan - Getty Images)
By January W. Payne
Washington Post Staff Writer
Tuesday, May 29, 2007

A report last week tying the Type 2 diabetes pill Avandia to increased risk for heart attack and heart-related deaths prompted a flood of calls to local doctors and Internet postings from patients seeking advice about whether to continue taking the commonly prescribed medication.

Stephen Clement, an endocrinologist at Georgetown University Hospital, said his clinic had fielded about 30 calls by Friday from patients taking Avandia, which increases the body's sensitivity to insulin, thereby helping to better control blood sugar levels. Clement advised patients to stay on the drug. But for those uncomfortable doing that, the clinic's "general response was that if they want to change, there's an alternative drug," Actos, which has a "similar onset of action and similar efficacy," he said. "We're leaving that up to them as an option if they want to change over."

Clement and other experts contacted said it's too soon to pull all patients off Avandia, based on the results of one study, a meta-analysis released last week by the New England Journal of Medicine. That advice didn't change even after U.S. Sen. Charles Grassley (R-Iowa) complained that the Food and Drug Administration was aware months ago of potential heart risks with Avandia and failed to act on an internal recommendation that the drug receive a black box warning, the agency's strongest warning label.

GlaxoSmithKline, the maker of Avandia, said in a statement that it "stands firmly behind the safety of Avandia when used appropriately, and we believe its significant benefits continue to outweigh any treatment risks."

"I think that the findings certainly raise concern, but I think that our response has to be a careful one," said Howard Baum, a Dallas endocrinologist who is chairman of the clinical affairs committee of the Endocrine Society. "There is more to be learned, and we have to be very careful about switching people to a new medication without understanding the full implications of such a switch." (GlaxoSmithKline is a member of the society's Corporate Liaison Board. Baum said he has no ties to the drug industry.)

Here are experts' answers to some common questions about the development:

I take Avandia. Should I stop? Should I switch to another medication?

Switching may not be necessary, and you certainly don't want to stop before you consult your doctor. Diabetes, a chronic disease characterized by high blood sugar levels that affects more than 20 million Americans, poses the risk of complications, including hypertension, nerve damage and heart disease, so it's important to keep the condition under control. Many doctors are recommending that patients stick with their current treatment regimen. Experts also note that all medications carry a risk of side effects, so the benefits of taking any new drug must be weighed against its potential for adverse effects.

Patients should recognize that switching to another medicine "is not risk-free, both because the NEJM study's findings might represent a class effect" -- meaning the heightened risk, if verified, might also apply to Actos -- "and because the impact of any drug substitution can be unpredictable," the Endocrine Society advised in a statement.

What are the drug options if I stop taking Avandia?

Treating diabetes requires an individual plan that takes into account your personal medical history, lab results and other medications you may be taking.

Some doctors are switching patients to Actos, which like Avandia is athiazolidinedione. Actos and other medications can be used alone or in combination to treat Type 2 diabetes. Those other drugs include:

· Sulfonylureas, which "stimulate the beta cells of the pancreas to release more insulin," according to the American Diabetes Association.

· Meglitinides, which also stimulate cells to release insulin.

· Biguanides, which lower blood glucose, mostly by limiting how much glucose is produced by the liver. Metformin, a commonly prescribed drug that helps regulate the amount of sugar in blood, is contained in this class.

· Alpha-glucosidase inhibitors, which help lower blood glucose by stopping the breakdown of starches and some sugars.

· Injectable medications including Symlin and Byetta.

· Insulin is often used as a last resort after pills have failed to control Type 2 diabetes. Some diabetics combine insulin with pills to treat their conditions.

Has Avandia been withdrawn from the market? Will I have trouble filling a prescription for it if my doctor deems it safe to continue?

Avandia is still available. The FDA issued a "safety alert" last week advising that Type 2 diabetics, "especially those who are known to have underlying heart disease or who are at high risk of heart attack, should talk to their doctor" to evaluate treatment options.

Will researchers continue to study Avandia to investigate heart risks?

Yes. A large study, called the RECORD trial, is ongoing. And the FDA is still analyzing all available data to determine what, if any risk, may be involved in taking the drug.

If I have heart disease or it runs in my family, am I at increased risk for complications from taking Avandia?

Experts can't say for sure. But some doctors said the new report isn't enough to sway them to switch all patients at high risk for heart problems. "My personal practice is that I'm not going to recommend automatically that somebody change medications because of these findings," including those with heart disease or a family history of heart problems, Baum said.

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