In fact, at that time, some 85 cases of liver failure had been linked to patients
using Rezulin and of these, 56 diabetics died. (by
2003, it was suspected by the FDA that 400 cases of death from liver
failure were connected to this medication. The FDA issued a formal warning about Avandia in 2007 - and by 2008, there were many lawsuits from injured patients and researchers were advocating recall of these medications.)
March 7, 2000
Patients, Doctors Not Warned of Dangers of
New Diabetes Drugs
Public Citizen Petitions FDA to Revise Labels
for Three Drugs
WASHINGTON, D.C. -- The U.S. Food and Drug Administration (FDA)
should immediately revise labels on three new diabetes drugs to warn
doctors and patients that the drugs are of questionable effectiveness
and can have serious side effects, Public Citizen said in a
petition to the FDA.
The drugs, Rezulin, Avandia and Actos, are in a class of drugs called
"glitazones." The drugs are used to treat type 2 diabetes, a less severe
form of the disease in which patients do not require outside sources of
insulin. Glitazones are used to help patients improve their sensitivity
to their own insulin. An estimated 15 million people in the U.S. have
type 2 diabetes.
Studies have shown that adverse effects of the three drugs can
include liver damage, heart damage, weight gain, fluid retention, low
blood pressure, anemia and possible changes in hormone levels, Public
Citizenís petition says. In addition, studies show that the three drugs
are less effective than older drugs. However, this information is either
omitted or underplayed in the current label.
These problems were well known to FDA medical officers who reviewed
the drugs before they were approved. The medical officersí reviews,
transcripts from advisory committee meetings, and Public Citizenís own
reviews of the medical literature form the basis of the petition. Dr.
Sidney M. Wolfe, M.D., director of Public Citizenís Health Research
"It is outrageous
that this critical information is being kept from doctors and
patients. They need to be aware of the dangers associated with these
drugs. These drugs have extremely serious adverse effects and are not
as effective as some of the older drugs."
One of the drugs, Rezulin, was pulled from the market in 1997 by British
medical authorities because of 130 cases worldwide of liver damage,
including six deaths. According to a recent
statement by the FDAís director of the drug review center, 58 deaths
attributed to Rezulin have now been reported to the U.S. agency.
Public Citizen petitioned the FDA in 1998 to ban Rezulin. According to a
knowledgeable FDA physician, a large proportion of physicians at FDA
familiar with Rezulinís dangers think the drug should be taken off the
The petition states that:
Results in nine of 10 studies showed that the three drugs were
less effective than older drugs. Blood sugar level deteriorated when
patients were switched from old drugs to these new drugs;
The FDA has received reports that patients using Rezulin had
higher rates of heart failure than patients on older drugs used to
treat diabetes. In just the first 18 months that Rezulin was on the
market, the FDA listed 56 cases of heart failure associated with the
drug compared to only four cases reported over a period of 13 years
for glucotrol (a sulfonylurea), an older diabetes drug;
The new drugs led to weight gain in various studies of an average
of two to 12 pounds;
Some patients using the drugs experienced fluid accumulation in
their legs and lungs.
One FDA medical officer wrote,
"I am concerned
that long-term exposure to [Avandia] may give rise to a similar liver
problem as with [Rezulin]" -- that is, the liver failure that drove
Rezulin from the market in Great Britain.
Two published reports have already documented severe liver damage in
patients taking Avandia, but none of the information is in the label,
Public Citizenís petition says.
Anemia was another side effect not adequately addressed in the
labels, the petition says. The drugsí labels mention anemia under
"laboratory abnormalities" but dismiss its significance. Although an FDA
medical officer wrote of the potential for patients to develop anemia
when taking Avandia along with another type 2 diabetes drug with which
it is frequently used, the label states that there is no increase in
anemia with that drug combination.
Similarly, the labels state that fluid retention occurred in animal
and human studies of the drugs, but the labels lack a discussion of the
reasons. Without that information, doctors may treat fluid retention
with drugs such as calcium channel blockers that could be harmful when
taken with the glitazones.
Weight gain was a common problem for all three drugs and appears to
be related to how the drugs work in the body. Weight gain puts patients
at higher diabetic risks, yet an FDA medical officer wrote that "[Avandia]
appears to lower glucose levels by converting glucose to fat."
"Doctors likely will prescribe these drugs inappropriately because
they have not been provided any of this critical information," Wolfe
said. "That could seriously jeopardize patient health. The FDA should
act immediately for the sake of diabetic patients throughout the
Physicians were initially intrigued with Rezulin and like medications
because earlier medications for diabetes type II overworked the pancreas
to produce more insulin and eventually, the pancreas failed, resulting in
the diabetic needing to inject insulin on a daily basis. Rezulin forces
the insulin resistant cells to become less insulin resistant.
The best treatment for diabetes type II especially in the early stages,
seems to be lifestyle changes of a low fat, low sugar diet and daily
exercise. (Exercise has been proven to make cells less insulin
Rezulin, a drug prescribed to maintain blood sugar
levels in patients suffering from adult-onset diabetes, was approved by
the FDA in 1997. Initially thought to be a breakthrough for patients who
failed to respond to other therapies, the FDA later disclosed that at
least 61 patients taking Rezulin died of liver failure, while another
seven required liver transplants. New concerns have surfaced about
Rezulinís detrimental effect on the heart. The FDA has since revised its
estimate and now suspects that Rezulin may be linked to more than 400