Women who take two widely prescribed drugs to treat diabetes may face an
elevated risk of hip, arm and other bone fractures, new research reveals.
Rosiglitazone and pioglitazone, sold under the brand names Avandia and Actos,
seem to accelerate bone density loss and create a heightened threat of fracture
among women - especially seniors - who have taken them over a long period of
time. The same risk was not seen in men, or among women who took other drugs to
manage diabetes.
"This is one of the strongest skeletal toxicity agents we've seen," said Sonal
Singh, assistant professor of internal medicine at Wake Forest University in
North Carolina and co-author of the study. "It's a substantial risk factor and I
don't think we've recognized that."
The results highlight weaknesses in the way drug problems are reported and how
the potential risks are disseminated to the medical community, Dr. Singh said.
"The current mechanism has really failed to disclose these kinds of risks," he
said.
Robert Spanheimer, medical director for diabetes at Takeda Pharmaceuticals North
America Inc., which sells Actos, said the company has gone to great lengths to
ensure health professionals and the public know of the potential risks.
"We've gotten the information to health-care providers. We've told them what to
look for," he said. "I think we've responded as quickly as possible."
He said that, based on the company's analysis, the fracture risk doesn't appear
to be great. He said there is about one fracture for every 125 years of patient
exposure to Actos.
The company is conducting its own long-term study to understand how the
medication may contribute to a woman's fracture risk and how great that risk may
be.
GlaxoSmithKline Inc., which markets Avandia, also said it has publicized the
potential side effects, and that it "closely monitors safety for all of its
products." The company is also conducting a trial to determine the link between
the drug and fracture risk.
The findings, released today in the Canadian Medical Association Journal, are
another knock on the already-controversial drugs.
Avandia and Actos are thiazolidinediones, a class of drugs used to treat Type 2
diabetes, help control blood sugar and decrease resistance to insulin. But
questions have been raised about their safety in recent years, leading some
advocates to call for their removal from the market.
Previous studies have found Avandia is associated with a heightened risk of
congestive heart failure, heart attack and death among older diabetics.
Actos has also been associated with a heightened risk of heart problems.
Health Canada has issued warnings about both of the drugs, including
restrictions on when and how Avandia should be prescribed.
The link between the diabetes drugs and bone fractures has been noted in the
past and the drug companies have issued warnings to consumers.
But the new study is considered to be the largest and most definitive analysis
of available data that show Avandia and Actos can lead to higher risk of
fractures.
Researchers examined 12 previously published studies involving thousands of
participants to determine the level of risk.
They found that one out of every 20 postmenopausal women who took the drugs for
at least one year would suffer a medication-linked fracture. "It is
substantial," Dr. Singh said.
Over all, 111 of 1,903 women who took Avandia or Actos suffered fractures,
compared with 76 of 2,497 women who did not take those drugs. Among men, only 64
of 3,064 had a fracture while taking a thiazolidinedione.
The most common fractures suffered by women were in their arms and legs, Dr.
Singh said.
Researchers say the risk to women may be the result of enzyme differences
between genders.
None of the studies were designed specifically to examine the link between the
diabetes drugs and bone fractures, which represents a potential limitation of
the findings.
However, even though the studies weren't set up to measure fractures, they still
found a heightened fracture risk, which demonstrates the potential threat is
real, according to a Canadian scientist who has done extensive research on the
safety of thiazolidinediones and the possibility they increase the risk of heart
problems.
"We may need to be considering the use of this drug more seriously," said
Lorraine Lipscombe, endocrinologist at Toronto's Women's College Hospital and
scientist at the Institute for Clinical Evaluative Sciences.
But the findings also reveal a flaw in the way drug companies design clinical
trials when seeking approval for a new medication, Dr. Lipscombe said.
"Clinical trials are often underpowered to detect adverse effects, particularly
ones that are unexpected," she said. "People should be more systematically
looking for harms."
