Drug for diabetes is linked to heart risks

FDA issues safety alert

drugmaker contests research

May 22, 2007|By Chris Emery and Jonathan Bor | Chris Emery and Jonathan Bor,SUN REPORTERS

Researchers say an oral diabetes drug used by millions of Americans may increase the risk of heart attack and cardiovascular death, prompting federal drug safety officials yesterday to encourage patients to consult their doctors.

Patients who took Avandia, a relatively new drug that lowers diabetics' blood sugar, were at 43 percent higher risk of heart attack and 64 percent higher risk of cardiovascular death than patients who took other drugs or a placebo, according to a review of previous research released yesterday by The New England Journal of Medicine.

Avandia generated $3 billion in sales last year, and nearly 60 million prescriptions for the drug have been issued since it was approved by the Food and Drug Administration in 1999.

Although diabetes experts cautioned that the study results were preliminary, they said doctors should consider prescribing alternative medications or reserving use of Avandia and similar drugs for patients for whom other therapies are no longer effective.

"I'm not convinced to stop using them," said Dr. Christopher D. Saudek, director of the Johns Hopkins Diabetes Center. "But the clinical lesson is not jumping in with the newest drug - use more established drugs more, and brand-new drugs less."

GlaxoSmithKline, the drug's manufacturer, contested the findings of the study done by the Cleveland Clinic.

"GSK strongly disagrees with the conclusions reached in the ... article, which are based on incomplete evidence and a methodology that the author admits has significant limitations," Glaxo said in a prepared statement. Its stock price declined $4.53, closing at $53.18.

The company cited two of its own studies that found no significant increase in heart complications. But a spokeswoman did acknowledge that a company review of other studies found that Avandia patients had a 30 percent to 40 percent increased risk of heart attack than those taking placebo or other diabetes drugs.

Around 20 million Americans have Type 2 diabetes, and it is estimated to be the sixth leading cause of death in the United States, according to the National Institutes of Health.

People with Type 2 diabetes either produce too much blood sugar, don't produce enough insulin or their cells ignore insulin, a condition known as insulin resistance, which prevents the cells from processing sugar. This causes sugar to build in the bloodstream, which over time can damage a person's eyes, kidneys, nerves and heart.

Avandia - the trade name for the drug rosiglitazone - belongs to a class of drugs known as insulin sensitizers, which make cells more responsive to insulin. The other insulin sensitizer available is pioglitazone, which is manufactured by Takeda Pharmaceutical Co. and sold under the name Actos.

The drugs work by activating genes that regulate cellular metabolism of sugars and fats, which makes the cells more sensitive to insulin. Previous studies have shown the sensitizers are effective at lowering diabetics' blood sugar levels.

The authors of the study released yesterday did not conduct an original experiment but instead reviewed evidence from 42 separate trials that compared the drug with other treatments or placebo.

"The results of this analysis raise serious concerns about the cardiovascular safety of rosiglitazone," said Dr. Steven Nissen, chairman of the Cleveland Clinic's Department of Cardiovascular Medicine and lead author of the study.

The effect of a diabetes therapy on the heart is of critical importance, he said, because more diabetics die of heart disease than of any other complication.

"Unfortunately, rosiglitazone appears to increase, rather than decrease, the most serious complication of diabetes, heart disease," Nissen said in a prepared statement.

Hopkins' Saudek said one possible explanation for the increased risk of heart disease could be the drug's side effects, which include fluid and salt retention, and weight gain.

Yesterday, the FDA issued a safety alert, saying patients taking Avandia - especially those with underlying heart conditions - should consult their doctors about the potential risks.

But the agency is not asking Glaxo to take any specific action at this time because it had not confirmed the significance of the study's findings. In a statement, the agency said that while the Cleveland Clinic review found a significant increase in cardiovascular risks, an interim report from a large, ongoing trial has found no such effect.

Dr. Steven Galson, director of the FDA's center for drug evaluation, said the agency wanted to assess whether pioglitazone, the other drug in the class, posed similar or greater risks. Also, he noted that there is an "inherent risk" in switching from one diabetes drug to another.

"FDA will take the issue of cardiovascular risk associated with Avandia and other drugs in this class to an advisory committee as soon as one can be convened," Galson said.

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