NBC video
Updated Video Research: Diabetes drug increases heart attack risk
May 21: New research shows that a widely prescribed diabetes drug,
Avandia, increases heart attack risk by 43 percent. NBC’s Robert Bazell
reports and Dr. Jerry Avorn from Harvard Medical School offers analysis.

Updated: 2 hours, 47 minutes ago

A widely used diabetes pill raises the risk of heart attacks and
possibly death, according to a scientific analysis that reveals what
some experts are calling another Vioxx-like example of the government
failing to protect the public from an unsafe drug.

More than 6 million people worldwide have taken the drug, sold as
Avandia and Avandamet, since it came on the market eight years ago to
help control blood sugar in people with the most common form of
diabetes. About 1 million Americans use it now.

Pooled results of dozens of studies on nearly 28,000 people revealed a
43 percent higher risk of heart attack for those taking Avandia compared
to people taking other diabetes drugs or no diabetes medication,
according to the analysis published online Monday. The study, published
by the New England Journal of Medicine, also found a trend toward more
heart-related deaths.
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Especially hazardous link
The findings are frightening because two-thirds of diabetics die of
heart problems, so a drug that boosts this possibility is especially
hazardous for them.

Still, the actual risks to any single patient appear small. Diabetics
should talk to their doctors before stopping any medication, said a
statement issued by the American Diabetes Association and two groups of
heart doctors.

Avandia’s maker, British-based GlaxoSmithKline PLC, disputed the results
of the analysis but acknowledged that its own similar review found a 30
percent increased risk — information it gave last August and possibly
even earlier to the U.S. Food and Drug Administration. But the company
said that more rigorous studies did not confirm excess risk.

FDA officials issued a safety alert on Monday and said they likely would
convene an advisory panel, but planned no immediate changes to the
current side effect warnings on the drug’s packaging.

Several members of Congress expressed alarm. Rep. Henry Waxman,
D-Calif., chairman of the House Committee on Oversight and Government
Reform, announced a hearing for June 6 on FDA’s role. On the Senate
floor, Charles Grassley, R-Iowa, criticized the agency for not acting
more swiftly.

Another Vioxx?
“Do we have another Vioxx on our hands with Avandia? I am not sure, but
I intend to find out,” he said, referring to the blockbuster arthritis
drug withdrawn in 2004 because of safety problems. “Tens of millions of
prescriptions have been written for Avandia, and Medicare and Medicaid
have paid hundreds of millions of dollars for this drug.”

Avandia is used to treat Type 2 diabetes, the most common form of the
disease, which is linked to obesity and afflicts 18 million Americans
and 200 million people worldwide. This form of diabetes occurs when the
body does not make enough insulin or cannot effectively use what it
manages to produce.

Avandia, or rosiglitazone, helps sensitize the body to insulin and was
considered a breakthrough medication for blood-sugar control. It also is
combined with metformin and sold as Avandamet. Only one other drug like
it — pioglitazone, sold as Actos and Actoplus Met by Takeda
Pharmaceuticals — is sold in the United States.

Avandia had total U.S. sales of $2.2 billion in 2006, slightly trailing
$2.6 million for Actos, according to IMS Health, a healthcare
information company. About 13 million Avandia prescriptions were filled
in the U.S. last year. A one-month supply of Avandia sells for between
$90 and $170.

GlaxoSmithKline also has been testing Avandia to try to prevent diabetes
in those at high risk of it, and, in separate studies, to prevent
Alzheimer’s disease.

However, the new analysis casts a pall on its prospects for prevention
as well as treatment, many specialists said. The study was led by Dr.
Steven Nissen and statistician Kathy Wolski at the Cleveland Clinic.
Nissen accepts no personal fees for consulting for any drug makers.

While the analysis doesn’t spell out the actual the rate of heart
attacks among Avandia users, the 43 percent excess risk is in line with
what a similar analysis found for lower doses of Vioxx use, Nissen said.
Another context for that number: Heart attack risks are lowered about 25
percent by cholesterol-reducing statin drugs — ample reason to prescribe
them.

The Avandia studies Nissen analyzed were not designed to look for heart
risks and many of them were so short — some only 24 weeks — that risks
may only appear over the longer term, he said.

Dr. David Nathan, chief of diabetes care at Massachusetts General
Hospital, agreed.

“This analysis is just scratching the surface of what may be there. It
needs to be taken seriously,” said Nathan, who reviewed the paper for
the medical journal and has no financial ties to any diabetes drugmakers.

The situation “reflects very badly on the FDA and on Glaxo,” Nathan
said. “It’s the FDA’s responsibility to be monitoring this stuff.”

‘Major failure’
The drug “represents a major failure of the drug-use and drug-approval
processes in the United States,” Drs. Bruce Psaty and Curt Furberg wrote
in an editorial in the New England Journal. Psaty is with the University
of Washington in Seattle and Furberg is with Wake Forest University.

When the drug was approved, evidence of its benefits were “at best
mixed,” wrote the two doctors. Both have been frequent critics of the
FDA’s failure to spot dangers in the drug approval process and its
conduct involving Vioxx.

Avandia’s label already warns about possible heart failure and other
heart problems when taken with insulin. The drug also raises LDL or bad
cholesterol, and can cause fluid retention and weight gain. Glaxo also
has reported some patients suffered more bone fractures, swelling of the
legs and feet, and rare reports of swelling in the eye that can cause
vision problems.

However, in a conference call Monday, Dr. Lawson McCartney who leads
Glaxo’s diabetes drug development, said: “We remain very confident in
the safety and of course in the efficacy of Avandia as an important
diabetic medicine.”

Dr. Robert J. Meyer of the FDA’s Center for Drug Evaluation and
Research, also defended the agency’s actions, saying information about
risks is not clear-cut.

“We’ve tried to weigh the risks of going forward with an uncertain
message … with the level of uncertainty about the safety signal before
us,”

Glaxo’s shares trading in the United States closed down $4.53, or 7.9
percent, at $53.18.

Nissen used publicly available information from an earlier $2.5 million
Glaxo settlement with the state of New York to do his study. He also led
earlier research that derailed a similar diabetes drug, Pargluva, that
seemed headed for FDA approval until safety issues emerged. A fourth
drug in the same class, Rezulin, was withdrawn in 2000 after it was
linked to liver problems.

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