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The National Alzheimer’s Project Act: Don’t Forget

Renee Despres
Friday, June 15, 2012 - 20:33

The popular diabetes drug Avandia (generic name rosiglitazone), made by GlaxoSmithKline, is once again the focus of media attention as a panel of government experts and medical advisors debate the relative benefits and risks of the drug. An FDA panel is scheduled to rule today on whether to keep the drug on the market, and if so, what labeling and other restrictions should be applied to it. The debate has generated scathing critiques of drug companies, calls for reform to the FDA’s post-approval processes for scrutiny of drug safety, and critiques of physicians who continue to prescribe Avandia despite the evidence linking the drug to heart damage.

Update: The Avandia saga continues, with no clear verdict. The outcome of the 33-member panel’s vote, as reported by the New York Times: 12 members voted that Avandia should be withdrawn; 10 voted that sales of the drug should be restricted and warnings on its label enhanced; 7 voted only that warnings on the drug’s label be enhanced; and 3 voted that the drug should continue to be sold with its present warnings. One member abstained. The final option, to weaken the label’s present heart warnings, received no votes. It’s now up to the FDA to make sense of this confusing set of recommendations.

Avandia is often prescribed for people with type 2 diabetes. It works to make cells in the body more sensitive to insulin, thus lowering blood sugar levels by allowing sugar to enter the cells. Avandia was once one of the top-selling drugs in the world. Sales were a cool $3.2 billion in 2006. By 2009, however, sales had dropped to $1.2 billion, as study after study raised concerns about whether Avandia causes heart damage, stroke, and death.

This week’s debate was prefaced last Friday by an unusually strong statement by FDA official Thomas Marciniak, M.D. Marciniak minced no words in a scathing critique of a large (4,447 patients) clinical trial known as RECORD, which was conducted by GlaxoSmithKline beginning in 2001 at the request of the European Medications Agency. In a detailed analysis of the study design and results, Marciniak found that GSK had undercounted cardiovascular events, especially heart attacks, that occurred in the group of people who were taking Avandia. Marciniak concluded that the RECORD trial “was inadequately designed and conducted” and that the study both confirms and extends already recognized concerns about Avandia and heart failure, and that the drug increases the risk for heart attack. GSK, however, maintains that the study shows that there was no increase in cardiovascular events for patients taking Avandia compared to two other popular drugs, metformin and sulfonylurea.

Marciniak’s analysis was prompted in part by a long line of research suggesting that Avandia is linked with heart damage. Questions about Avandia’s safety first made headlines in May 2007, when Steven Nissen, chair of cardiovascular medicine at the Cleveland Clinic, and coauthor Kathy Wolski published findings that suggested Avandia increased users’ risk of heart attack. After Nissen and Wolski’s results appeared in The New England Journal of Medicine, a committee of independent experts (many of whom at the table today) found that Avandia might increase the risk of heart attack but recommended that it remain on the market. An FDA oversight board concurred with that advice, voting 8 to 7 in favor. the FDA issued a warning

In February 2010, FDA, in confidential reports obtained by the New York Times, concluded that nearly 500 heart attacks and 300 cases of heart failure could be avoided every month if the people currently taking Avandia were instead taking another drug, Actos. From July to September 2009, 309 deaths were linked to Avandia.

It gets worse. GSK executives – and some FDA officials – still hold that the benefits of the drug outweigh the risks. Yet GSK executives have known about Avandia’s effects on the heart for more than a decade, according to internal company documents obtained by the New York Times. These documents showed that results of a trial that began in 1999 had linked Avandia with substantial risk of cardiovascular events. According to Times reporter Gardiner Harris, “instead of publishing the results, the company spent the next 11 years trying to cover them up…. The company did not post the results on its Web site or submit them to federal drug regulators, as is required in most cases by law.”

Harris quotes from an e-mail message dated March 29, 2001, written by GlaxoSmithKline executive Dr. Martin I. Freed: “This was done for the U.S. business, way under the radar. Per Sr. Mgmt request, these data should not see the light of day to anyone outside of GSK.”

Well…. ouch. We all knew that GlaxoSmithKline wasn’t the icon of benevolence. But GlaxoSmithKline obviously violated the unstated contract between pharmaceutical companies and consumers. That contract goes something like this: Drug companies get to make lots of money, have happy shareholders, and their executives get to buy yachts. In return, they carry out enough well-designed clinical trials to guarantee that the products they sell are reasonably safe and have the desired effects. We trust drug companies to share information about just how big the risks of a drug are in comparison to the benefits. Consumers get to take drugs to fix their health problems, with some clear estimate of the risks involved. We trust regulatory agencies to oversee that process. But — as the ambivalent verdict shows — that contract broke down badly in the case of Avandia. Even after 11 years of widespread use, there are not enough data for a panel of “experts” to make a clear decision about whether to leave Avandia on the market.

Every drug we use – alcohol, caffeine, aspirin, herbal remedies, or Avandia – involves risks. Sometimes the risk of not taking the drug is greater than the risks involved in taking it; sometimes vice versa. Remember that until 1922, a diagnosis of diabetes was a death sentence. But in the case of Avandia, there’s another pharmaceutical option — Actos — which appears to be equally effective for people with type 2 diabetes and much less risky. In addition, nonpharmaceutical interventions, including diet and exercise, can significantly alter the body’s ability to use insulin with minimal risk.

While the debate rages, what should you do if you’re taking Avandia to control your type 2 diabetes?

  • Do not quit the drug. Schedule an appointment with your doctor
  • Explore other ways to control your blood sugar. If you’re having difficulty controlling your blood sugar level, ask your physician about other pharmaceutical and lifestyle options that can help with blood sugar control.
  • Ask to make an appointment with a certified diabetes educator (CDE). CDEs are highly-trained professionals specializing in diabetes prevention and management who can offer practical advice about living with diabetes.