Study on Avandia by GlaxoSmithKline Questioned by Physicians
A recently released clinical study intended to test whether GlaxoSmithKline PLC’s diabetes drug Avandia may be harmful to the heart appears to have raised more questions than it has answered, as some doctors claim that the study is flawed.
Safety concerns have troubled Avandia since 2007, when an analysis of the medication suggested that people taking it had a higher chance of suffering a heart attack than people taking other diabetes pills. Avandia and other diabetes drugs are designed to control blood-sugar levels, which can reduce a person’s risk for cardiovascular disease.
Results of a large, Glaxo-funded trial published in the medical journal The Lancet on June 5, 2006 showed that people taking Avandia didn’t have a higher risk of being hospitalized or dying from cardiovascular problems than people taking other drugs for Type 2 diabetes, an outcome that Philip Home, chairman of the study’s steering committee and a professor at Newcastle University, said “provides a robust assessment of [Avandia's] cardiovascular safety.”
The study “provides important and reassuring information about Avandia for physicians fighting diabetes,” said Ellen Strahlman, Glaxo’s chief medical officer. But a pair of doctors writing an editorial in the Lancet said “definitive conclusions” about Avandia’s effects on the heart “remain elusive” because of the study’s “limitations.”
The 4,447 patients in the study, called Record, were split into two groups. One group received Avandia plus one of two older diabetes drugs; the other received the two older drugs in combination. They were followed for 5 years.
In their editorial, the endocrinologists Ravi Retnakaran and Bernard Zinman of Mount Sinai Hospital in Toronto said the rate of cardiovascular problems in the trial was lower than expected, making it difficult to draw firm conclusions.
One potential reason, they said, was that a significant number of people in the Avandia group took cholesterol-lowering statins, which are known to reduce a person’s risk of heart attacks or other cardiovascular problems.
A relatively high level of patients dropping out of the trial may also have compromised the results and led to a lower than expected number of cardiovascular problems, some physicians said. According to Glaxo, about 45% of participants dropped out of the trial at some point. Some physicians said this could have happened because of the negative publicity surrounding Avandia.
A Glaxo spokeswoman said the dropout rate did not affect the primary aim of the study, which was to show that Avandia didn’t increase the risk for death or hospitalization due to cardiovascular problems.
Concerning heart attacks specifically, there were 60 cases in the Avandia group versus 52 in the other group, a difference that could have been due to chance, the study’s authors said, calling the evidence about heart-attack risks “inconclusive.”
David Robbins, a professor of medicine at Kansas University School of Medicine, said the Record trial may have been too small to generate enough cardiovascular events to show for certain whether Avandia is riskier than other drugs.
He also expressed disappointment that Avandia didn’t improve cardiovascular outcomes. “What we really want in diabetes is that these drugs are reducing cardiovascular events,” he said. “Lowering blood sugar is not enough.”
The study confirmed previously known risks related to Avandia that are already noted on the drug’s prescribing label.
