Avandia Side Effects May Have Hurt or Killed 100,000 People: Draft Study

A draft study by an FDA scientist has linked side effects of Avandia to tens of thousands of heart problems among elderly users, and suggests that more than 100,000 Americans may have suffered heart attacks, strokes or other problems from Avandia since the drug was introduced.

The draft Avandia study (pdf) was performed by drug safety reviewers from FDA and the Centers for Medicare and Medicaid Services (CMS). According to a story by Pharmalot, a drug reviewer at the FDA is pushing for the study to be published in a medical journal in the near future, while the FDA is continuing its own analysis of the safety of GlaxoSmithKline’s diabetes drug.

The researchers performed an observational study looking at data from more than 227,000 Avandia users over the age of 65 and compared those with users of the competing diabetes drug Actos, by Takeda Pharmaceuticals. They found that in that age group, Avandia increased the risk of stroke by 27%, the risk of heart failure by 25%, and the risk of death by 13%. Overall, the researchers estimated that 48,000 elderly users experienced an event attributable to Avandia side effects.

“Given that 62% of [Avandia] use has been in patients below age 65, the actual national impact is probably 100,000 or more,” the researchers concluded.

Avandia (rosiglitazone) was approved in the United States in 1998 to treat type 2 diabetes by helping control blood sugar levels. The drug has been used by millions of diabetics, but sales have plummeted in recent years as concerns have mounted about the risk of serious and potentially life-threatening heart risks with Avandia.

Concerns about the risk of Avandia heart problems first gained widespread attention in May 2007, when a meta-analysis of 42 different clinical trials was published in the New England Journal of Medicine, suggesting that users of Avandia had a 43% increased risk of a heart attack.

Earlier this year, a Senate report on Avandia accused GlaxoSmithKline of suppressing the risks of Avandia, and indicated that many within the FDA have been calling for a recall of Avandia. Following the release of the scathing report, the FDA announced that it is still reviewing safety data on the drug and indicated that conclusions will likely not be released until later this summer.

In recent months, there have been calls from consumer advocates and researchers for the FDA to halt a new Avandia health risk study, suggesting that it is unethical and dangerous for the trials to continue given the known risk of problems with Avandia. Critics are also concerned that many of the test subjects are being recruited in developing countries where people may not be as informed about Avandia problems.

In April, FDA Commissioner Margaret Hamburg sent a letter to U.S. Senator Charles Grassley indicating that the agency is considering shutting down the comparative study over concerns about the ethics of continuing the trial. Many have speculated that if the FDA deems exposing clinical subjects to potential Avandia heart problems unethical, it will likely lead to an Avandia recall for the same reasons.

GlaxoSmithKline PLC currently faces about 13,000 Avandia lawsuit claims filed by former users of the drug who allege that the drug company failed to adequately research their medication or warn users about the serious side effects. The federal Avandia litigation has been consolidated into an MDL, or Multidistrict Litigation, for pretrial litigation in the U.S. District Court for the Eastern District of Pennsylvania.

Over the last two months, GlaxoSmithKline has reached Avandia settlements in about 5,700 of those lawsuits for undisclosed amounts.