On May 21, 2007, a study published in the New England Journal of Medicine raised questions about the safety of GlaxoSmithKline’s diabetes drug Avandia. Dr. Steven Nissen with the Cleveland Clinic analyzed 42 clinical trials involving the drug, known generically as rosiglitazone, and concluded that the drug increased the risk of heart death by 64 percent and the risk of heart attack by 43 percent.

Avandia is widely used to treat type 2 diabetes by keeping blood sugar levels within a safe limit. Approved by the U.S. Food and Drug Administration (FDA) in 1999, Avandia has been prescribed to approximately 60 million patients.

Diabetic patients are especially susceptible to heart disease because diabetes can damage the heart muscle and advance the formation of potentially fatal blood clots.

“Cardiovascular disease is far and away the leading cause of death in diabetes,” Dr. Nisssen said. “If you find a diabetes drug increases the risk of heart attacks, the consequences are so grave that it warrants urgent action.”

The FDA has advised diabetes patients taking Avandia to discuss the new information with their doctors as well as possible alternative therapies. Patients should not stop taking any medications without first consulting their doctors.

The study’s findings are based on analysis of published data from previous clinical trials comparing the risk of heart attack and heart disease-related death in those who took Avandia with patients who took a placebo. The analysis, involving almost 28,000 patients in clinical trial studies that lasted between six months and one year, discovered that more than 65 percent of the deaths of patients in the drug trials could be attributed to heart disease. There were 158 heart attacks and 61 deaths from heart complications in the studies.

GlaxoSmithKline presented its own study of the drug to the FDA in August 2006, in which it found a cardiovascular risk of about 30 percent. This risk percentage, however, was not confirmed by long-term or observational studies.

Dr. Nissen is a cardiologist and chairman of cardiovascular medicine for the Cleveland Clinic, one of the most prestigious heart clinics in the United States. In 2001, he co-authored an analysis of Vioxx that found an increased risk of heart attack or stroke in patients. Merck recalled the drug in September 2004 after its own study confirmed the risk.

Dr. Nissen also published an article in 2005 speaking about concerns he had with Pargluva, a diabetes drug that a Food and Drug Administration (FDA) panel supported. The FDA ultimately declined to approve the drug.

After his Pargluva study, Dr. Nissen received an email from a diabetes expert who suggested that Avandia undergo analysis as well. He began studying Avandia in 2006, initiating congressional investigations and researching previous studies published by GlaxoSmithKline.

While researching, he found a study similar to the one he was conducting performed by GlaxoSmithKline. The study also showed slightly elevated risks of heart attacks, but the company wrote that these risks were manageable and no conclusion could be drawn from their study.

The Food and Drug Administration (FDA) has not confirmed that Avandia increases risks for heart death or disease.

For more information, consumers can visit GlaxoSmithKline’s Avandia website, or call GlaxoSmithKline’s Customer Response Center at 1-888-825-5249 between 8 a.m. and 8 p.m. Monday through Friday.

Sources: Julie Steenhuysen, “Glaxo’s Avandia raises heart-death risk: study,” Reuters, May 21, 2007; Stephanie Saul, “Study cites safety questions about diabetes drug,” New York Times, May 21, 2007; Michelle Fay Cortez, “Glaxo’s Avandia May Raise Heart-Attack, Death Risks,” Bloomberg.com, May 21.