June 7, 2013
An expert panel has recommended loosening restrictions on the diabetes drug rosiglitazone (Avandia). The panel based its advice on a new analysis of a study about the drug's effect on heart attack risk. Avandia was a huge seller before researchers raised questions about its effects on heart health. One major study pooled results of 42 previous studies. It concluded that people taking Avandia had a higher risk of heart attack than people taking other diabetes drugs. A later study directly compared heart attack rates for people taking different diabetes drugs. That study found no increased risk with Avandia. But critics questioned how well it was done. In 2010, the FDA sharply restricted access to the drug. Both doctor and patient must acknowledge they know the risks and cannot lower blood sugar enough with other drugs. Prescriptions plummeted. The new study takes a new look at the 2010 study. The FDA ordered the study. GlaxoSmithKline, maker of Avandia, paid for it. Duke University researchers examined each case. They found no increased risk with Avandia. Of the 26-member expert panel, 13 voted June 6 to loosen the prescribing rules. Seven voted to remove them. The FDA usually follows the advice of its expert advisers. The Associated Press wrote about the issue.
By Howard LeWine, M.D.
Harvard Medical School
What Is the Doctor's Reaction?
The heart attack and stroke risk of rosiglitazone (Avandia) and other diabetes drugs is an important issue. That's because heart disease is the most common cause of death among people with diabetes. More than 23 million Americans have diabetes. And the number is growing fast.
The Avandia story is one of a boom and bust for GlaxoSmithKline, the company that makes and sells it. The original studies of Avandia were very positive. They led to approval by the U.S. Food and Drug Administration (FDA) in 1999.
People with type 2 diabetes could achieve better blood sugar control with Avandia. And they could do this without weight gain. Weight gain was a major drawback of other diabetes drugs. Avandia rapidly became a big money maker for Glaxo.
Within a few years, some people taking Avandia were retaining fluid. Doctors already knew that Avandia could make advanced heart failure worse. Fluid build-up is a common problem in heart failure. But the problem with Avandia was actually bigger than that. About 1 out of 5 older adults retained fluid while taking the drug. Many of them did not have heart failure.
The problem of fluid retention was not limited to Avandia. This drug belongs to a class of diabetes drugs commonly called glitazones. For example, pioglitazone (Actos) has the same side effect. People with heart failure should not take either drug.
In 2007, the view of Avandia started to change. People taking Avandia got something extra to worry about. Was the drug they took to control blood sugar harming their hearts?
During the next few years, the evidence about Avandia's heart attack and stroke risk mounted. In 2010, the FDA recommended that Avandia be used only when other treatments did not achieve blood sugar control. Around the same time, the European Medicines Agency recommended that all use of the drug be stopped.
In May 2011, the FDA came close to pulling the drug from the market. Instead, it imposed major restrictions. Pharmacists could no longer stock Avandia. It could be obtained only by special order. For someone to receive the drug, both doctor and patient had to sign a waiver. This statement said that they understood the heart risks and that other treatments were not working or caused too many side effects.
GlaxoSmithKline had to accept the changes. But the company's experts maintained that the drug's heart and stroke risk was the same as for other diabetes drugs. And for people without heart failure, they claimed that risk was extremely small, if it existed at all. People with diabetes are already at higher risk for heart attacks and strokes.
Research looking at the risks continued. Now a new FDA panel of experts has taken a new look at the evidence.
Most of the experts conclude that the restrictions on Avandia are too strict. Half of them (13) want to loosen the restrictions. Another seven want them to be removed completely. But five of the experts disagree. They say the restrictions should stay in place. One expert wants the drug taken off the market.
The full FDA usually follows the advice of the expert panel.
What Changes Can I Make Now?
The reason for the early excitement about Avandia has not changed. Avandia targeted a major problem in type 2 diabetes -- insulin resistance.
Insulin normally helps the sugar in our blood get into the liver and muscles to provide energy. In type 2 diabetes, the liver and muscle cells don't respond well to the insulin. The sugar can't get into the cells. This is called insulin resistance. As a result, sugar in the blood starts to rise.
The pancreas responds by putting out more insulin to try to push the sugar into liver and muscle cells. This starts a cycle of higher blood sugars and higher blood insulin levels. Eventually, the pancreas can't keep up with the rising blood sugars.
Lifestyle changes offer the best ways to decrease insulin resistance:
If lifestyle changes alone aren't enough to lower blood sugar, a person with type 2 diabetes may need drug treatment. Most doctors prescribe metformin. It is available as a generic, so it is relatively low in cost. It decreases insulin resistance and improves blood sugar control. Usually there's no weight gain.
What Can I Expect Looking to the Future?
The FDA has approved several new drugs for type 2 diabetes in the last few years. However, potential serious side effects for some of them already have been raised.
All diabetes drugs lower blood sugar levels. But most of them have not been proven to directly improve health. And long-term safety remains a question.
Metformin is the exception. That's why it remains the best first choice for type 2 diabetes drug treatment.
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