FDA Moves to Loosen Restrictions on Diabetes Drug Avandia

At a Food and Drug Administration (FDA) hearing in June 2013, the agency signaled a willingness to relax some of the restrictions it had previously placed on rosiglitazone (AVANDIA), the diabetes drug banned in Europe due to its serious cardiovascular risks. This move comes despite a lack of any new evidence lessening safety concerns.

Rosiglitazone remains categorized as Do Not Use at WorstPills.org.

Recent actions

When the European Medicines Agency (EMA) banned rosiglitazone in September 2010, it stated that the drug’s benefits no longer outweighed its significant cardiovascular risks. The EMA said the ban would last until drug company GlaxoSmithKline (GSK) could “supply convincing data to identify a patient population in which the clinical benefits of rosiglitazone-containing medicines clearly outweigh their risks.” Three years later, no such evidence exists, and so the European ban remains in place.

Using the same safety studies that prompted the EMA’s ban, the Food and Drug Administration (FDA) decided in September 2010 to leave rosiglitazone on the market, restricting its use through a program designed to make the drug available to those who might benefit from it. GSK had not then — and has not since — identified such a group.

Between the EMA ban and the implementation of the FDA’s restricted use program, approximately 130,000 Americans used this dangerous drug, likely resulting in hundreds or more serious — even fatal — adverse reactions, including heart failure and heart attacks.

By 2012, the restricted use program had reduced the number of users in this country to 2,400.

At the June 2013 FDA hearing, the only new safety information presented was a review confirming the findings of one study that helped prompt the EMA’s ban. At this same hearing, GSK stated that there is “a positive [benefit-to-risk] profile for rosiglitazone for the treatment of type 2 diabetes in appropriate patients.” However, the company has thus far been unable to persuade the EMA that this patient population exists.

Earlier history

The history of rosiglitazone demonstrates increasing concern about the drug’s heart toxicity. Before it was approved in 1999, studies of the drug in animals prompted an FDA reviewer to state, “Pharmacology recommends not to approve rosiglitazone for the proposed indication for long-term human use.”

Shortly after rosiglitazone’s approval, Public Citizen petitioned the FDA to revise the labeling to reflect its risks, such as heart failure. As further evidence of increased cardiac risk became known, the 2005 edition of the Worst Pills, Best Pills book labeled the drug as Do Not Use.

At an FDA hearing in 2007, Public Citizen testified that rosiglitazone should not be allowed on the market and one year later filed a formal petition with the agency to ban the drug. In a very unusual move, the American Diabetes Association and the European Association for the Study of Diabetes have concluded that for the treatment of diabetes, “given that other [treatment] options are now recommended, the consensus group members unanimously advised against using rosiglitazone.”

Internal FDA memos that were later made public show that those with the most knowledge about drug safety within the agency agreed that the drug should be banned. In 2009, Dr. Gerald Dal Pan, Director of the FDA’s Office of Surveillance and Epidemiology, wrote that “the benefits of rosiglitazone do not outweigh its risks. I recommend granting the [Public] Citizen petition’s request that FDA remove rosiglitazone from the market.”

The 2010 FDA decision not to ban the drug but to restrict its use occurred despite many advisory committee members recommending a ban. At an FDA advisory committee meeting in July 2010, 12 of the 32 members voted to take rosiglitazone off the market. Their reasons included: “There may be a few patients who do very well on rosiglitazone, but I can treat them other ways, and all the other endocrinologists can.” Another stated that “from a public health perspective, it seems to me that it’s a benefit that can be obtained from another drug … . It’s pretty clear that the public would be best served by not having the drug available.” A third stated that “we should apply the same standards as if this drug were coming up for approval. If it were coming up for approval, I have not seen data that would convince me it ought to be approved.”

At the 2013 meeting, despite the lack of any new evidence of rosiglitazone being safer, the FDA and GSK helped persuade a majority of the advisory committee to vote in favor of relaxing the previous restrictions.

It also is relevant to note that in August 2012, as part of a record $3 billion U.S. fine for criminal and civil violations, GSK agreed to pay a $242,612,800 criminal fine related to withholding from the FDA information about the drug.

What You Can Do

Do not use rosiglitazone. If you are among those diabetics still using the drug, talk with your doctor about switching to a more effective, safer, less expensive alternative, such as metformin.

If you are a diabetic not currently taking rosiglitazone, make sure that you side with the EMA, doctors in Europe and, most importantly, European patients by saying no to becoming a potential victim of the use of this risky drug.

The article “Diabetes Drugs Linked to Pancreas Disease” in the August 2013 issue of Worst Pills, Best Pills News advised not to use any of the so-called GLP-enhancing drugs, such as exenatide (BYETTA, BYDUREON), liraglutide (VICTOZA), sitagliptin (JANUVIA, JANUMET, JANUMET XR, JUVISYNC), saxagliptin (ONGLYZA, KOMBIGLYZE XR), alogliptin (NESINA, KAZANO, OSENI) and linagliptin (TRADJENTA, JENTADUETO). There is increasing evidence that these drugs cause pancreatitis and probably pancreatic cancer.