Sunday, April 26, 2009

Unsafe? Avandia for Diabetics

There have been a succession of disappointments about drug therapy in recent years. One drug, Avandia, became a popular diabetes medication. It took several years and a brave MD to uncover evidence that it is not such a good drug, after all.

Avandia is rosiglitazone, a popular diabetes 2 drug. Doubts were raised about the safety of this drug and there are arguments for and against it. The arguments and concerns will not be resolved quickly. Avandia is marketed by Glaxo, which, like all drug companies, vigorously defends its big money drugs. Sales of Avandia reached $3.2billion per year in the US.

Our perspective for 2 decades is that the drug treatment of diabetes lacked convincing long-term efficacy and there were important concerns about side effects and long-term adverse effects. Oral medications should not be considered as primary treatment. However, MDs tend to be drug prescribers, drug companies are interested in making money and patients are obedient consumers who like to believe there are simple solutions for complex problems.

Dr. Steven Nissen and colleagues from the Cleveland Clinic reviewed more than 40 studies and concluded that Avandia increased the risk of heart attacks by 43 percent. Psaty and Furberg recalculated Nissen’s analysis using interim results of the Record study in addition to the studies that Nissen used. They found that Avandia increased a patient’s risk of having a heart attack 33 percent. Nissen is an experienced but independent FDA advisor who has become an ombudsman for the American people.

In the US where Avandia was developed and concerns were announced, questions about the safety of Avandia and how regulators have dealt with its risks were asked at Congressional hearing in June 2007. Glaxo had an ongoing study, REPORT, and rushed to submit favorable interim results for publication in advance of the government hearing.

In his New England Journal editorial, Dr. David M. Nathan, a Harvard diabetes expert, doubted the value of the REPORT study because of the high number of patients who dropped out and the study design which compared Avandia to a combination of metformin and sulfonylurea. While this combination is popular, doubts about its safety were raised and never resolved in another study that showed a 96 percent increase in diabetes-related mortality. Metformin alone appears to be relatively free of cardiovascular risk. Nathan concluded that the interim results of the Record trial do not provide any assurance of the safety of treatment with rosiglitazone and suggested that doctors should use medications other than Avandia.

A series of drug adverse effect withdrawals in recently years have generated criticism, that the US Food and Drug Administration fails to protect the public. In the Avandia case, critics say that the US FDA should have warned about the potential heart risks years ago. A supervisor in the drug safety office at the agency said in an interview that she was rebuked after calling for a stronger warning label on Avandia and a competing drug, Actos.

November 20, 2007: A US Senate Committee on Finance released a report describing what it terms the "intimidation" of Dr John Buse by GlaxoSmithKline (GSK) over his concerns about the cardiovascular risks associated with the company's antidiabetes drug rosiglitazone (Avandia). The committee stated: "According to documents provided to the committee by, among others, GSK and the University of North Carolina, it is apparent that the original allegations regarding Dr Buse and GSK’s attempts at silencing him are true. According to relevant emails, GSK executives labeled Dr Buse a 'renegade' and silenced his concerns about Avandia by complaining to his superiors and threatening a lawsuit."

The main problem for a growing number of patients is the false belief that a drug or combination of drugs can rescue an individual from a disease-causing lifestyle. While there may be benefits to be had with medications, a person with diabetes 2 should learn expert self-management skills and exercise all the therapeutic and preventative options available before taking drugs.

From the Book Managing Diabetes 2 by Stephen Gislason MD

See further discussions of medical biases and limitations

Also See Diabetes Drugs