Avandia Slammed In Another Study
3 CommentsBy Ed Silverman // July 18th, 2007 // 7:47 am
A new meta-analysis of 18 studies finds that Glaxo’s diabetes pill doesn’t “positively influence” the health of diabetics, reduce death, improve quality of life, but does contribute to weight gain, swelling, heart risks and broken bones, according to an analysis published by the Cochrane Library, which examined trials with more than 8,000 diabetics on Avandia, placebo or rival drugs for 24 weeks or more.
“We found out that we don’t influence patient-oriented outcomes” by prescribing Avandia to diabetics, Bernd Richter, a professor at Heinrich-Heine University in Dusseldorf, Germany and co-author of the article, tells Bloomberg News. The Cochrane Library is published by the Cochrane Collaboration, a non-profit organization that reviews evidence about drugs.
Richter went on to say the findings support the May report in The New England Journal of Medicine, and that regulators should consider granting restricted approvals that require drugmakers to continue safety studies after meds reach the market. The FDA will review Avandia at a July 30 meeting.
Ron Krall, Glaxo’s chief medical officer, argues the review doesn’t provide new evidence and is based on a limited number of studies that generate misleading conclusions, such as a six-month time frame isn’t long enough to fully analyze deaths or complications that occur over longer periods. “The analysis would be more informative if it recognized the benefits that are demonstrated in short-term studies of glucose lowering and also recognized what has been shown in the longer term studies,” Krall tells Bloomberg News.
The review of Avandia was assigned to the German research team last year, Richter says. He and his colleagues included the results of a Glaxo-funded study called ADOPT that enrolled more than 4,000 diabetics and was published in the New England Journal of Medicine last year. The Cochrane review cited data from that study. Richter said it showed Avandia increased the risk of heart and circulatory conditions more than generic medicines metformin or glyburide.
Glaxo has tried to be very aggressive in defending Avandia, taking out full-page newspaper ads and threatening lawyers over ads soliciting clients. Yesterday, Glaxo distributed a statement to journalists in advance of the Cochrane study in which the drugmaker also tries to defend its record in releasing clinical trial data, although critics have noted the drugmaker only did so after being forced by the former New York attorney general. Here’s the statement…
“This review is another analysis of existing data that have previously been reported. Glaxo believes that the limited number of studies evaluated generate misleading conclusions and provide no new evidence about the use of rosiglitazone in clinical practice and research.
The review includes 18 already existing studies and does not include all data available on Glaxo’s Clinical Trial Register. Rosiglitazone (Avandia) has been studied in one of the largest programs ever undertaken to evaluate the safety and effectiveness of a medicine (52,000 patients) and the largest for any oral anti-diabetic medicine to date.
Furthermore, the studies included in the review primarily measured differences in blood glucose control over the short term, not mortality or morbidity outcomes. It is therefore not surprising that positive conclusions were not drawn on this outcome.
The conclusions regarding increased cardiovascular risk are not substantiated by the totality of the existing data on rosiglitazone. The authors performed their own meta-analysis on myocardial infarction rates and could not confirm any significant difference in risk between rosiglitazone and control groups.
Questions about the safety of rosiglitazone should be answered by reviewing the totality of the evidence, in particular long-term prospective studies. In ADOPT, all major adverse cardiovascular events (MACE) were analyzed and such events were rare in this population and comparable for all treatments - rosiglitazone, metformin and glibenclamide. Furthermore, RECORD, the only study specifically designed to look at cardiovascular outcomes, was not included in the review. Though RECORD is ongoing, the interim findings do not show evidence of a difference in cardiovascular death between rosiglitazone and control groups and showed no significant difference for heart attack.
The review concludes that no clinically relevant differences regarding metabolic control were noted between rosiglitazone and other anti-diabetic therapies. The conclusion is drawn primarily from a limited number of short-term studies, when clinical guidelines have highlighted the importance of maintaining long-term glycaemic control. ADOPT, the only long term study (4-6 years) that compares rosiglitazone with metformin and glibenclamide found that rosiglitazone maintained glycaemic control for longer than these commonly used agents (a 32 and 63 percent risk reduction of monotherapy failure compared to metformin and glibenclamide respectively).
Glaxo strongly disagrees with the authors’ conclusion which questions the ethics of starting new studies with rosiglitazone. We are committed to patient safety and carry out our clinical trials with the highest level of ethical conduct. The totality of the data - including long-term studies such as ADOPT and RECORD and an epidemiological analysis of more than 33,000 patients in a US managed care database - show that rosiglitazone has a comparable ischaemic cardiovascular profile to other oral anti-diabetic medicines. Glaxo stands firmly behind the safety profile of rosiglitazone when used appropriately.
Glaxo is strongly committed to full transparency of our scientific information. We have actively shared our data on rosiglitazone with regulatory agencies worldwide as quickly as scientifically possible. We have updated the rosiglitazone label over time in order to help physicians appropriately care for their patients. Data is made available to scientists in the public domain in a variety of ways, including postings on our Clinical Trial Register, which GSK was one of the first to develop and contains results from 114 clinical trials on rosiglitazone.
Dr. Remulac
This is absolutely nothing new, and yet it gets picked up by major news outlets. The other drug in the TZD class, Actos, would demonstrate the EXACT same results if anyone were to actually analyze it. Lilly/Takeda are flying under the radar with Actos right now, hoping that no one will notice and ask the same questions of their drug. Meanwhile, they are raking in huge profits due to patients being switched from Avandia to Actos by clueless prescribers who have fallen prey to Takeda’s shady selling/marketing practices. Avandia and Actos are expensive drugs that DO NOT provide substantial clinical benefit over cheaper, older, generic drugs like metformin, but they do carry clearly higher risks related to CHF and weight gain. The July 30 FDA safety review of the TZD class is going to be a joke. They loaded the panel with “experts with an axe to grind with Avandia/GSK while they are being funded via research dollars by Actos/Takeda. Don’t expect this review to do anything more than continue to inappropriately villify Avandia while leaving Actos relatively unscathed.
Melody
Dr. Remulac–
You state: ” Lilly/Takeda are flying under the radar.”
This is the MO for Lilly. They did it with their rDNA human insulin. They claimed it was “better” than natural animal insulins (no proof) and they claimed it was “just like the human body makes” (again, no proof). But just as today, clueless prescribers fell prey, and shady selling practices and marketing tactics (think anti-trust, here) were used, and ignored by media, by medical professionals, and by watchdog agencies. Ho-hum–business as usual!!!
Rita Goode
Another drug… “approved and deemed to be safe for us to consume by the FDA “. Is this really a surprise to anyone?
Since the Pharmaceutical companies are , in reality, running the FDA, they are basically approving their own drugs. Again, it is the almighty dollar over the consumers safety and health, and again, we are prohibited from buying Canadian drugs because THEY “are not safe”. Hah!
I have never been one to take any kind of pills other than aspirin, until I was diagnosed in May of 2005. I am a diabetic who took Avandia for a year. then ceased taking it after learning more about the FDA and the claims of Glaxo about Avandia.
The more that is learned about the FDA’s “review” and so-called “testing” of medications to be released, the less I trust any entity that is hiding behind a veil of “government”, when in all actuality, these entities are soley driven by political influence, not government “oversight”. There is an enormously descernable difference between the two.
The “testing” of theses drugs seems to be…. passing the “marketablity test”, and the “how long can we sell it until a study finds out the truth?” test.
We are not innocent in this vicious circle. The more we allow the labels of “syndrome” and “disease” to be attached to common conditions that have other cures that do not involve drugs, and we accept the doctors who gain financially by being the legal “pushers” of these drugs, the more we, the public, are to blame as well.
We are told, by our own government officials, that those who smoke marijuana are guilty in the trafficking of ILLEGAL narcotics, simply by buying them from the dealers, therefore, giving them a reason to keep supplying. Apply this opinion to the pharm’s and the FDA, as well. The only difference is, these drugs are deemed LEGAL, therefore the pharms are LEGAL dealers of LEGAL drugs, because…guess what, make a list of who profits and who benefits from the sale of these “safe”, LEGAL drugs.
The next time you have a problem helath-wise, just ask your doctor if he is a “pill Doctor”, or a medical doctor. He will not be offended if he can actually claim to have a medical interest in your health, more so over his pockets being lined.
Just for fun, check out the medical benefits of BANANAS!