F.D.A. Issues Strictest Warning on
Two Diabetes Drugs
By GARDINER HARRIS
Published: June 7, 2007
WASHINGTON, June 6 — The Food and Drug
Administration has called for the toughest safety
warning on two diabetes drugs, Avandia and Actos,
whose health risks have become a focus of
That decision, disclosed on Wednesday by the F.D.A.
commissioner at a packed House hearing, comes more
than a year after the agency’s safety reviewers
strongly recommended just such a step. And it occurs
amid a Congressional investigation into why the
agency delayed its warnings about Avandia for years.
In a written statement, the commissioner, Andrew C.
von Eschenbach, said the agency has asked the makers
of Actos and Avandia to carry the more prominent
warning, a so-called black box warning, of its heart
risks because “despite existing warnings, these
drugs were being prescribed to patients with
significant heart failure.”
The statement said the agency requested the label
changes on May 23, which was two days after a
medical journal article and editorial about
Avandia’s potential heart risks set off the current
controversy. Word of the label changes, however, had
not been made public before Wednesday’s hearing.
Dr. Rosemary Johann-Liang, a drug safety supervisor
for the agency, had said in an interview this week
that she was reprimanded last year for advocating
the very label change that Dr. von Eschenbach said
the agency was now asking the drug companies to
make. Avandia, a Type 2 diabetes treatment made by
GlaxoSmithKline, has been the focus of most of the
recent safety concerns, based on evidence that it
can potentially cause heart attacks or other
cardiovascular problems. But its closest competitor,
Actos, a drug from Takeda Pharmaceuticals and Eli
Lilly & Company, has also been seen as carrying some
risk of problems, including heart failure.
The makers of both drugs said that they were
discussing the new warnings about heart failure with
the drug agency. “This is generally a process that
takes weeks to months,” said Dr. Robert Spanheimer,
a senior medical director at Takeda.
Democrats on the House panel voiced harsh criticism
of the drug agency and Dr. von Eschenbach, whom the
Bush administration named commissioner in September
Representative Henry A. Waxman, a California
Democrat who is chairman of the panel, the House
Committee on Oversight and Government Reform, said
the agency had “dropped the ball” in its oversight
of Avandia’s safety. The agency should have insisted
years ago that Glaxo test whether Avandia increased
the risks of heart attacks, Mr. Waxman said.
“Avandia is a case study of the need for reform of
our drug safety laws,” Mr. Waxman said. “F.D.A.
needs the will, the resources and the authority to
be a more effective watchdog of drug safety.”
Democrats asked Dr. von Eschenbach if he believed
his agency needed more authority from Congress to
require drug makers to perform safety studies or
correct drug advertisements. Dr. von Eschenbach said
his agency required more money, not authority. And
he characterized as “more destructive than
constructive” proposals by some of the agency’s
Congressional critics to separate the F.D.A.’s drug
approval and drug safety functions.
Some Republican members of the committee criticized
Democrats on the panel for making too much of
uncertain information about Avandia, a popular
diabetes pill that has been taken by an estimated
seven million people worldwide.
Representative Virginia Foxx, Republican of North
Carolina, said she was concerned that those studying
the drug had spoken to Democrats on the committee
but not to anyone at the drug agency.
“I’d like members of the press to investigate what
members of Congress knew about this” and whether
those members joined some F.D.A. staff members and
others “to create maximum embarrassment to the
agency,” Ms. Foxx said.
Representative Darrell Issa, Republican of
California, said the committee was coming
dangerously close to “politicizing science.” And he
closely questioned Dr. Steven E. Nissen, a
cardiologist at the Cleveland Clinic whose May 21
article in The New England Journal of Medicine
questioned the safety of Avandia.
“This does look like in fact that this was a
political concoction to anecdotally go after a
company, and I object to it,” Mr. Issa said.
As with most hearings involving the F.D.A., members
of Congress sometimes seemed bewildered by some of
the technical answers given by witnesses on
Wednesday, and several lawmakers stumbled over
medical terms at the heart of the debate.
The agency officials themselves appeared confused
when Representative Stephen F. Lynch, Democrat of
Massachusetts, asked the three agency witnesses to
look at Avandia’s drug label and find its warning
about heart attacks.
“Have you found it yet?” Mr. Lynch kept asking.
Dr. von Eschenbach deferred to Dr. John K. Jenkins,
head of the F.D.A.’s office of new drugs. Dr.
Jenkins eventually referred to a small table in the
“That’s it?” Mr. Lynch asked. “You’re not seriously
telling me that that’s it.”
Dr. von Eschenbach said that the agency was in the
process of improving the readability of all drug
Representative Diane E. Watson, Democrat of
California, said she had diabetes and had been
taking Avandia until her doctor told her that she
had developed a heart murmur.
“My doctor said, ‘Get off of Avandia — there are
other options out there,’ ” Ms. Watson said.
She told Dr. von Eschenbach that warnings about such
heart problems should be prominently displayed on
the drug’s label.
“You ought to have heart attack on the label, and I
believe I was heading toward just that when I went
to my physician,” Ms. Watson said.
Dr. von Eschenbach said the F.D.A. was studying the
data to decide whether to do that.
Dr. John B. Buse, an endocrinologist at the
University of North Carolina School of Medicine and
the incoming president of the American Diabetes
Association, said that when he spoke publicly in
1999 about his fears that Avandia might increase
heart risks, he was threatened in phone calls from
the drug’s maker.
“During those calls, it was mentioned on two
occasions that there were some in the company who
felt that my actions were scurrilous enough to
attempt to hold me liable for a loss in market
capitalization” of $4 billion, Dr. Buse said.
“I was characterized as a liar,” Dr. Buse said. “I
was characterized as being for sale.”
Dr. Moncef Slaoui, chairman of research and
development for GlaxoSmithKline, said in his own
statement that he was “extremely disappointed” by
editorials published Tuesday in The New England
Journal of Medicine questioning Avandia’s safety.
Dr. Slaoui said he and the company “strongly believe
that the overall safety of Avandia is comparable to
other available oral anti-diabetes medicines.”