Steven Nissen, MD
Steven Nissen, MD, chairman, department of cardiovascular medicine, Cleveland Clinic. He has more than 35 years of experience as a physician and is world-renowned for his work as a cardiologist, patient advocate and researcher.
What a mess — that’s the best way I can describe the latest ruckus around the drug Avandia (rosiglitazone). Astonishingly, the most commonly prescribed diabetes medication is now known to raise the risk for heart disease, which itself is one of the most serious health consequences of having diabetes. This is a cautionary tale for our times, rife with corporate greed, medical shortsightedness and, not for the first time, an appalling lack of oversight by the FDA.
How did all this happen, you might wonder? I was able to get the whole story from the doctor who is at the center of the controversy, Steven Nissen, MD, chairman of the department of cardiovascular medicine at the Cleveland Clinic. Dr. Nissen brought public attention to the dangers associated with Avandia in 2007, when he conducted a review of studies finding that the drug increased risk of heart attacks by 30% to 43%.
In 1999, the FDA approved GlaxoSmithKline’s new drug Avandia for treatment of diabetes. The drug, which works by increasing the body’s sensitivity to changes in insulin levels, had gone through numerous clinical trials involving thousands of patients — and even back then, several studies showed that it substantially increased LDL cholesterol. Dr. Nissen said that one study showed that the patients taking Avandia had almost twice as many “ischemic myocardial events” (including heart attack, angina and hospitalization for chest pain) as the patients taking other diabetes therapies. This was particularly worrisome given that the trials were short-term, typically 24 weeks — whatever damage the drug did happened quickly.
So why was Avandia approved? Solely because of its effect on blood sugar, Dr. Nissen told me, calling this “shortsighted and scientifically unwise,” and noting that Avandia clearly had adverse effects that, for some patients, would overwhelm the benefit they’d get from taking the drug. Nonetheless, with GlaxoSmithKline’s considerable resources behind it, Avandia quickly became the biggest-selling diabetes medication, though another drug (Actos/pioglitazone — a drug of the same class made by a different company that was introduced around the same time) works as well and is safer.
Meanwhile, having noticed that blip in cardiovascular events, Dr. Nissen and his colleagues set out to learn more, undertaking a meta-analysis of the data from 42 trials of Avandia, 35 of which had never been published. Their research efforts led the FDA to revisit the safety of Avandia, too. Both groups arrived at the same conclusion — there was an estimated 40% higher risk for heart attack among people taking Avandia than those taking other diabetes medications, including Actos, leading the FDA to issue a “black box” warning linking Avandia to elevated risk for cardiovascular events.
Dr. Nissen’s study results led to two new reports, both published this summer, calling yet more attention to the drug’s dangers. And now there is talk of doing away with Avandia altogether.
While many experts believe that Avandia presents an unacceptable cardiac risk and doesn’t work any better than Actos, others disagree. The FDA is weighing these mixed recommendations in determining whether to remove Avandia from the market. Dr. Nissen told me that he believes “the evidence is strong enough to warrant the drug’s withdrawal — it’s been strong enough for years.”
If you’re currently taking Avandia, don’t make a change on your own… but it may be time to call your doctor and ask the question that many experts have posed — why take a drug with serious risks when one without the risks will work as well?
Once more we’re left with evidence that the safety of the medications prescribed to vulnerable patients cannot be taken for granted. Drugs often have risks that are undisclosed, underplayed or clinically unappreciated — they too often end up making sick people sicker. The better solution, by far, is to solve the problem at its root. For people with type 2 diabetes, that usually means by addressing the lifestyle issues that underlie the illness — eat wisely, exercise more and control stress.