The drug giant GlaxoSmithKline’s controversial diabetes drug Avandia (generic name rosiglitazone) works by helping diabetics balance their blood-sugar levels. But since its inception, it has been found to increase the risk of heart attacks and strokes — and even death.
As many as 100,000 heart attacks, strokes, deaths and cases of heart failure may be directly attributed to Avandia since the drug was launched in 1999, according to FDA scientist Dr. David Graham. Yet physicians are still prescribing the drug to nearly half a million people, which translates into approximately $900 million in annual sales for GSK. How has this been allowed to happen? Let’s take a look at the history of this potentially lethal but still-legal drug, courtesy of PBS:
♦ May 25, 1999 – Avandia is introduced. Company buries an alarming study.
♦ December 27, 2000 – Companies merge to form GSK
♦ April 2001 – GSK begins study of Avandia
At the FDA’s request, GSK commissions RECORD, a large, six-year study comparing cardiovascular outcomes of Avandia to other commonly-used diabetes medicines. Critics of the study later say RECORD was inadequately designed and conducted to provide any reassurance about Avandia’s cardiovascular safety. GSK responds that the study results show no heart risks.
♦ June 2004 – Lawsuit results in GSK’s agreement to make all clinical trials available online
♦ 2006 – GSK reports $3 billion in annual sales of Avandia
♦ May 2, 2007 – Dr. Nissen discovers increased heart risks for patients taking Avandia
Skeptical of Avandia’s safety, Dr. Steven Nissen, chief cardiologist at the Cleveland Clinic, conducts analysis of 42 clinical trials of Avandia posted on GSK’s website. He and co-author Kathy Wolski submit an independent article to the New England Journal of Medicine stating that Avandia increases heart attack risk by 43 percent. A peer reviewer secretly faxes a copy to GSK.
♦ May 9, 2007 – GSK sets out to defend Avandia against Nissen’s findings
A GSK consultant acknowledges Dr. Nissen’s alarming conclusions regarding Avandia in an e-mail statement reproduced in a January 2010 report for the Senate Finance Committee. He concludes by saying:
“We cannot undermine the numbers, but I think they can be explained so we must concentrate on effective risk management.”
♦ June 14, 2007 – Nissen publishes his findings despite GSK’s efforts to stop him
Nissen and coauthor Wolski publish the peer-reviewed article of Avandia’s potentially dangerous side effects in The New England Journal of Medicine. Nissen decides to publish his analysis despite GSK executives’ efforts to persuade him otherwise in a secret meeting 11 days before publication.
♦ November 14, 2007 – FDA requires strong warning label for Avandia
During fierce Senate Finance Committee hearings led by Chuck Grassley (R-Iowa) and Max Baucus (D-Montana), senators accuse GSK of mishandling scientific evidence regarding Avandia and the FDA of having a conflict of interest with the drug. These hearings result in an FDA advisory committee reviewing Nissen’s research and GSK’s interim RECORD study.
The FDA ultimately allows Avandia to stay on the market with the addition of the FDA’s strictest “black-box” warning label.
♦ 2010 – Regulators stop Avandia sales in Europe because of the increased heart risks.
GSK takes a $2.4 billion charge in 2010 to cover litigation against it. Avandia sales drop to just $1.1 billion for GSK, down from $3 billion in 2006.
News Update: Glaxo Hit With $3.4 Billion Charge
January 18, 2011: GlaxoSmithKline has now taken $3.4 billion in charges to cover ongoing product-liability litigation and investigations into its handling of the controversial Avandia diabetes drug, which European regulators banned last fall because of its links to increased risk of heart attacks.This charge brings the company’s total charges of litigation to over $6 billion. For some perspective, according to a report from Pharmalot, the most recent $3.4 billion charge could wipe out the company’s financial earnings from the last quarter. The charge greatly exceeds Avandia sales, which have been declining, not surprisingly, due to the ongoing publicity about the side effects.
GSK is expected to release results of a large trial that was initially requested by the FDA in May 2010. The trial called TIDE is meant to determine whether Avandia causes heart problems. But critics want to stop the trial, worried it may lead to increase risk of deaths for participants. Some FDA staffers protested, for example, saying that the safety signals on Avandia were strong enough to make that trial unethical.
A revealing study presented at the American College of Preventive Medicine annual meeting by Dr. Mohammed Hassan Murad of Mayo Clinic reviewed 202 published medical journal articles that addressed the possible association between heart attack risk and Avandia in diabetes patients. Among journal article authors who concluded Avandia does NOT increase the risk, 86% had financial relationships with GlaxoSmithKline. Among authors of articles offering unfavorable reviews, only 18% had relationships with GSK.
Are you taking Avandia?
The product packaging warning warns: Avandia may cause serious side effects, including:
New or worse heart failure
- AVANDIA can cause your body to keep extra fluid (fluid retention), which leads to swelling (edema) and weight gain. Extra body fluid can make some heart problems worse or lead to heart failure. Heart failure means your heart does not pump blood well enough.
- If you have severe heart failure, you cannot start AVANDIA.
- If you have heart failure with symptoms (such as shortness of breath or swelling), even if these symptoms are not severe, AVANDIA may not be right for you.
Call your doctor right away if you have any of the following:
- swelling or fluid retention, especially in the ankles or legs
- shortness of breath or trouble breathing, especially when you lie down
- an unusually fast increase in weight
- unusual tiredness
Myocardial Infarction (“Heart Attack”)
Avandia may raise the risk of a heart attack. The risk of having a heart attack may be higher in people who take Avandia with insulin. Most people who take insulin should not also take Avandia.Symptoms of a heart attack can include the following:
- chest discomfort in the center of your chest that lasts for more than a few minutes, or that goes away or comes back
- chest discomfort that feels like uncomfortable pressure, squeezing, fullness or pain
- pain or discomfort in your arms, back, neck, jaw or stomach
- shortness of breath with or without chest discomfort
- breaking out in a cold sweat
- nausea or vomiting
- feeling lightheaded
Call your doctor or go to the nearest hospital emergency room right away if you think you are having a heart attack.
The Ethical Nag 
Last year GSK settled with the Feds for $3 billion over marketing issues. Doesn’t seem to have fazed them.
The underlying problem is lack of transparency in research with spinning of results and negative studies going missing. You should do an article on Tamiflu, Carolyn.
The other issue is the view of doctors and patients that drug treatment is better than lifestyle modification in conditions like diabetes. This is aggravated every time “targets” are lowered.Governments insurers and various foundations are culpable here.
Companies need to be held to account but others involved in health also need to accept they have a role.
Thanks Dr. Joe – I can almost understand why patients might prefer taking drugs to lifestyle modification. But I don’t get doctors who do not even attempt to make healthy behaviour counselling part of their practice. Here’s an exception: a colleague who’s very overweight recently had to have knee surgery, but her doc refused to recommend the procedure until she lost 30 pounds (due to the known issues around healing/complications). Now THAT’S lifestyle modification advice for you! PS I’m working on a Tamiflu article . . .