Avandia, Actos And Bone Fractures In Women
4 CommentsBy Ed Silverman // December 11th, 2008 // 7:10 am
The long-term use of the so-called glitizones, a popular class of diabetes pills that includes Glaxo’s Avandia and Takeda’s Actos, drugs doubles the risk of bone fractures in women with type 2 diabetes, according to a study in the Canadian Medical Association Journal.
The study reviewed 10 previous clinical trials, and for every 20 women in their 70s with type 2 diabetes who took the drugs for at least one year, one has a chance of suffering a fracture. In women in their mid-50s, the figure equals one fracture in every 55 women. That’s more than double the normal risk for those age groups.
An accompanying editorial concludes that “the ongoing accumulation of evidence of harm for (this class of drugs) is unsettling to clinicians and patients and threatens to undermine patient confidence.”
About 14,000 patients were involved in the studies analyzed by study co-author Sonal Singh, assistant professor of internal medicine at Wake Forest, and his colleagues. He notes the same increase in fractures was not found in men, although the reason was not clear.
In 2006, almost 4 million people in the US took the drugs pills, and Singh estimates about half were women, he tells USA Today, adding that the fracture risk and previously reported cardiovascular risks of the two drugs raise questions about the modest blood-sugar-lowering benefits of the class of drugs.
John Buse, president of medicine and science for the American Diabetes Association and a professor at the University of North Carolina-Chapel Hill, says the ADA recommends other drugs, such as oral metformin, as the first treatment options for people with diabetes. But, he tells USA Today, “there are some people who just can’t take metformin because it makes them vomit or have diarrhea.”
“You always weigh the good effects and ththe not-so-good effects,” says study co-author Curt Furberg, professor of public health sciences at Wake Forest.
He points out that researchers now know that the drugs increase the risk of heart failure and the risk of fractures in women. The FDA last year ordered black box warnings on both drugs’ labels against their use in patients with advanced congestive heart failure. Avandia has been shown to increase the risk of heart attacks as well.
“So it’s very much a gamble to take the drugs,” Furberg says.
Salmon
There are many, many, many drugs that cause skeletal problems. I only realized it several months ago but soon came to realize it’s so prevalent that companies had to know about it sooner.
Look at the labeling for many drugs and the preclinical fetal development studies you will see a pattern. Poor ossification, especially at the phylanges and where the ribs meet the sternum. It may get worse and show poor skeletal development and small pups, as well as a dimininshed number of pups.
These also will typically go together with human data showing prolongation of the QTc and sometimes hepatic fibrosis.
I suspect that this may have to do with effects on BMRP2 not only because it’s involved in bone growth and formation of fibrotic tissue but also mutations are associated with Pulmonary Arterial Hypertension.
Remember though if it’s labeled in the rabbits you’ll have no recourse to sue when your 88 yo mother places weight on her leg and it snaps and she tumbles down the stairs. The FDA will have reviewed it and says describing a little something about some rabbit digits not forming properly is enough of a warning for physicians to understand.
We wouldn’t want to overwarn anyone (espcecially small boned women) so they might switch to another agent that has less of effect on bone loss.
Salmon
Opinions are my own.
David M.
What did GSK know, and when did the company know it?
Salmon
David,
I don’t know. However simply going through labels in the PDR it’s so prevalent that I’m sure that all companies (as well as the FDA toxicologists) must have been aware of these patterns for decades. Even though the toxicologists said I was ‘out of my mind and there was no such signal the first time I realized it’. It’s only a matter of degree of severity. So if you know you have a QT signal and cardiac problem with the drug in humans then you know you probably also have a bone problem.
As for FDA. Last spring Janet Woodcock made an announcement about safety with fluoruquinolone antibiotics (e.g. ciprofloxacin) causing tendon rupturing and stating she wondered why (she was promoting her new safety initiative. Well it took me 5 minutes to figure out it was likely due to effects on BRMP2, which is associated with Pulmonary arterial hypertention, and guess what moxifloxacin if the positive control used for QT studies, and Trovafloxacin has a huge amount of hepatotoxicity (hepatic fibrosis - think Ketek). I’m really disgusted because the drugs I reviewed all had big QT problems along with I then realized problems with PAH and hepatic fibrosis.
I think FDA has known for a long long time and simply wasn’t telling the reviewers. The senior pharm/tox reviewers I found out knew and put it in reviews for other drugs but when I mentioned it in my review the pharm/tox review management dismissed my concerns and indicated in a counter review that I was full of it. I believe that this is falsification of government documents which is a crime. Of course the evidence has been turned over to the proper authorities. You need to contact congress and see why nothing is being done.
Salmon - A soon to be former FDA reviewer and whistleblower
Opinions are my own and do not represent the opinions of the FDA.
annieb
I beleive that the info regarding fluoroquinolones and tendon problems had been known for many years. Why is this being dragged out now? David as the above article mentions both GSK’s and Takeda’s products why are you singeling out GSK? Is your last name Nissen?