Two studies released Monday reported serious heart risks with GlaxoSmithKline Plc diabetes pill Avandia as U.S. regulators decide whether the drug should stay on the market.
An analysis of 56 clinical trials found Avandia increased the chances of a heart attack by 28 percent to 39 percent, researchers at the Cleveland Clinic in Ohio reported in an update to a 2007 study that sparked intense debate about the drug.
Dr. Steven Nissen, the lead author and an outspoken Avandia critic, said the results from more than 35,000 patients gave a more complete picture that reinforced his earlier concerns.
“A drug that increases the risk of heart attack by a third or more in diabetics represents a huge public health burden,” Nissen, the Cleveland Clinic’s head of cardiology, said in an interview. He said the drug should go off the market.
Glaxo shares fell 1.1 percent in London trading and nearly 1 percent on the New York Stock Exchange.
In another study released on Monday, government researchers said an analysis of more than 227,000 U.S. Medicare patients found Avandia was more dangerous to the heart than a rival pill, Takeda Pharmaceutical Co’s Actos.
Those findings, reported earlier this month by Reuters and others, were published online by the Journal of the American Medical Association. The study’s lead researcher is Food and Drug Administration reviewer David Graham, a whistleblower who has argued for years that Avandia is too risky.
Top FDA officials have disagreed, and Glaxo has vigorously defended the drug.
In February, the FDA said it was again reviewing Avandia’s risks and called an advisory panel meeting for next month.
The new studies are “important contributions to the discussion of Avandia’s safety,” FDA Deputy Commissioner Joshua Sharfstein said in an interview. The agency and the panel will consider those findings plus others, including FDA analyses not yet made public, he said.
The panel could urge keeping the drug on the market with a warning, or it could suggest a ban on future sales. The FDA usually follows panel recommendations.
The FDA, which approved Avandia 11 years ago, will “review all the available evidence and make the best possible decision,” Sharfstein said.
In the meantime, the agency has advised doctors and patients to continue using Avandia as directed. The current FDA-approved warning on Avandia says heart attack data are “inconclusive.”
Avandia’s use fell sharply after Nissen’s first study, but the medicine is still widely prescribed, with sales of $1.2 billion in 2009. It loses patent protection in 2012.
Glaxo now is facing lawsuits from patients claiming harm from the drug, known generically as rosiglitazone.
The company said six randomized clinical trials, the gold standard for medical studies, showed Avandia did not increase the overall risk of heart attack, stroke or death.
The studies released Monday are among the largest of Avandia, but they rely on a combination of multiple trials or past Medicare claims. Such studies are considered less reliable than randomized clinical trials.
In an editorial discussing Graham’s findings, Dr. David Juurlink of the Institute for Clinical Evaluative Sciences in Toronto argued for erring on the side of public safety in the face of uncertainty about risks.
“Accumulating concerns about (Avandia) make it difficult to advance a cogent argument why, exactly, a patient might want to receive the drug,” Juurlink wrote.
Many of the 23 million U.S. diabetics take medicines to lower blood sugar. The goal is to prevent disease complications such as blindness, amputations and heart disease, the leading killer of people with diabetes.
But critics say Avandia seems to contribute to heart damage. Nissen’s study, published by the Archives of Internal Medicine, estimated one more heart attack would occur for every 37 to 52 people who took the drug for five years.
Graham’s analysis, done with researchers at the FDA and the Centers for Medicare & Medicaid Services, found a 27 percent higher stroke risk for Avandia over Actos, a 25 percent greater risk of heart failure and a 14 percent higher chance of dying.
“In older Americans with diabetes, taking Avandia is detrimental to your health” and patients “are far better off taking (Actos),” Graham said in an interview.
Both Graham and Nissen have been asked to speak to the FDA panel, Sharfstein said.
Diabetics have many alternatives as 12 classes of drugs are approved to lower blood sugar, Nissen said. They include older generic drugs such as metformin and newer medicines such as Merck’s Januvia and AstraZeneca and Bristol-Myers Squibb’s Onglyza.
