If you weren’t paying careful attention last week you may have missed a very big FDA brouhaha over the diabetes drug Avandia. An FDA panel of experts did a U-turn and voted to ease restrictions on this controversial medication. What the heck is happening at the FDA?
A little history will help put this drug into perspective. A few years ago Avandia was riding high. In its heyday, it earned over $3 billion a year, making it the most successful diabetes drugs of all time. This medicine was marketed aggressively and doctors prescribed it enthusiastically.
Everything came to a screeching halt when cardiologist Steve Nissen, MD, of the Cleveland Clinic and his colleague, statistician Kathy Wolski, M.P.H., published an article in May of 2007 in the New England Journal of Medicine [NEJM] demonstrating a 43% increased risk of heart attack associated with Avandia use.
The spotlight immediately shone on Avandia and it became a highly controversial medication overnight. According to Dr. Nissen, the company was aware of potential cardiovascular problems associated with Avandia well before he published his NEJM article. Apparently the manufacturer even notified the FDA of an increased risk of heart attacks, but the agency chose to, in Nissen’s words, “conceal this hazard from patients and practitioners.”
When Nissen’s analysis made headlines and Congressional testimony corroborated his research, it created a dilemma for the FDA. In an article in Forbes, Dr. Nissen notes:
“The leadership of CDER [FDA’s Center for Drug Evaluation and Research] was intensely embarrassed by these revelations and furious with us for publicly challenging the safety of Avandia (and indirectly the competence and integrity of CDER). The FDA appeared incredibly insensitive to the welfare of patients. GSK knew, FDA knew, but patients and physician were not warned.”
Eventually, the FDA severely limited the use of Avandia to patients who could not tolerate other diabetes drugs. The manufacturer, GSK, paid a huge fine for suppressing some of the problems with Avandia. Drug regulators in Europe banned the drug outright. Case closed, right? Not so fast.
On June 5 and 6, 2013, the FDA reconsidered the safety of Avandia. The agency and GSK had asked Duke scientists to reanalyze the European data. In so doing, they concluded that there was no increased risk of heart attacks after all.
We won’t go into the complexity of the new analysis. Dr. Nissen, in his Forbes article, describes why this study (the RECORD trial) was flawed and “totally unreliable.” The reason: This was an “open-label” study in which both physicians and patients knew who was on Avandia and who was on placebo. Such trials are less convincing than double-blind studies where neither patients nor doctors know who is on the active medication.
The FDA expert panel reviewed the Duke data and recommended that restrictions on the drug be softened. GSK and the FDA may have felt vindicated by the panel’s decision. We, on the other hand, think that everyone has missed the point.
Patients with type 2 diabetes take drugs not just to lower their blood sugar. Laboraotry numbers are not as important as quality of life and survival. The point of the exercise should be to reduce the likelihood of complications from diabetes. Heart disease is one of the most important hazards of this metabolic condition. A diabetes medicine should, at the very least, lower the risk of heart attacks and other cardiovascular disorders dramatically. The best the Duke statisticians could manage, however, was a break even: no increased risk, but more importantly in our view, no reduced risk either! In our opinion, that is a huge failure of the medication.
But wait, there’s more. Avandia does have other side effects! No one is disputing that the drug increases the risk of congestive heart failure, a potentially fatal disorder. In addition, there is concern that the drug raises the chances of developing pneumonia and fractures.
AVANDIA (ROSIGLITAZONE) SIDE EFFECTS
- Headache
- Lung infections
- Fluid retention, edema, swelling in hands and feet, weight gain
- Shortness of breath
- Congestive heart failure
- Chest pain, angina, heart attack
- Liver damage
- Fractures
- Macular edema
- Severe skin reactions (require immediate medical attention!)
- Severe allergic reactions (require immediate medical attention!)
We cannot speak to the FDA’s motivations for revisiting the safety of Avandia. We can say, however, that a diabetes medication that does not lower the risk of heart attacks, strokes and early death is not high on our list of desirable drugs. For more information about how to lower blood sugar without medications and a overview of medicines that we think deserve your attention, see our Guide to Managing Diabetes.
Share your own story below and let us know what you think of the FDA’s recent reversal.
