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Some drugs just never go away, but they should
Last edited 15th June 2009
We first criticized this drug in 2006, when in the BMJ we first mooted rosiglitazone in the DREAM trial – which cost $23million - caused a significant increase in heart failure, despite the population being at low risk of such a problem. The drug showed no clear benefit at 3 years on clinical outcomes and the rate of all cardiovascular events tended to be higher in the treatment group.
What happened after that was good news, in that Steven Nissen in 2007 from the Cleveland Clinic undertook a systematic review of the effects of rosiglitazone, combining results from a total of 42 trials. The results clearly showed rosiglitizone was associated with a significant increase in the risk of heart attack and death confirming what we had suspected. Around the same time a Cochrane review also found there was no evidence of any benefits with the drug over other available treatments for diabetes and, because of side effects such as edema, fractures, and possible increased risk of MI, recommended other antidiabetic medications be used in preference.
The uses of composite end points in the DREAM trial were also aptly criticized by Victor Montori in the BMJ. These drugs were making significant inroads in the drug market with more than 1.5 million prescriptions for rosiglitazone and pioglitazone issued in England alone in 2007.
The week of the 5th of June, to my surprise the Lancet published the RECORD trial of rosiglitazone as an oral agent combination therapy. In English that means they combined it with another therapy. What they showed is rosiglitazone increased heart failure; but they then went on to report it doesn’t reduce cardiovascular death and the data was inconclusive on myocardial infarction rates. This is one of those interpretations designed to keep the drug on the market. Highly marketing driven and usually highly dangerous.
A couple of points however are worth noting: more people were on a statin (9%) in the rosiglitazone group, they had an excess of heart attack, and although this was not significant it adds to the findings in the Nissen systematic review. Also, in the subgroup of RECORD patients with pre-existing heart disease, there was a 26% increase in heart attack. In addition, it seems the treatment also raises the risk of fractures.
Finally, the RECORD trial had an unexpected low event rate, 2.5 % per year, whilst the trial was powered on an expected event rate of 11% per year; taken together with losses of 3% per year leads to very significant concerns about the results. The final nail in the coffin of this drug is that at the time of Nissen’s original review, approximately 30% of patients in the trial assigned to receive rosiglitazone had stopped taking the drug. By the time of the recent Lancet publication there is no mention of how many were actually on the drug. This is a no brainer, how can you assess the safety of a drug if you can’t tell who is actually taking it.
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BMJ take on the issue
BMJ now enters the fray
with a neat editorial from Deb Cohen
http://www.bmj.com/content/341/bmj.c4848
GlaxoSmithKline statement in response to FDA Advisory Committees
GlaxoSmithKline statement in response to FDA Advisory Committees’ vote on safety of Avandia® (rosiglitazone)
Women taking AVANDIA should know that AVANDIA may increase the risk of pregnancy. More fractures have been observed in women taking AVANDIA. Other possible side effects of AVANDIA include anemia and hypoglycaemia. Your doctor should do blood tests to check your liver before you start AVANDIA and during treatment as needed.
http://www.gsk.com/media/pressreleases/2010/2010_us_pressrelease_10059.htm
Pre-Meeting Posting of Slides for the July 13-14, 2010 Joint Mee
Pre-Meeting Posting of Slides for the July 13-14, 2010 Joint Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee
http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/E...
see Nissen's presentation for meta-analysis evidence
Glaxo Takes $2.4B Legal Charge On Avandia & Paxil
GlaxoSmithKline is trying aggressively to dispense with nagging and costly litigation and so will take a $2.4 billion charge in its second quarter to settle product-liability lawsuits over its Avandia diabetes pill, antitrust litigation involving the Paxil antidepressant and a US government investigation into its manufacturing site at Cidra, Puerto Rico. A breakdown was not provided, but Glaxo will pay $750 million to settle the probe into the plant, according to a statement................ more at
http://www.pharmalot.com/2010/07/glaxo-takes-24b-legal-charge-on-avandia...
Cheers CH
Former FDA Reviewer & Avandia: In Her Own Words
By now, the name Rosemary Johann-Liang may sound familiar. She is the former FDA medical reviewer who left the agency three years ago amid controversy over her work on GlaxoSmithKline’s Avandia diabetes pill (background links here). Johann-Liang had pressed for stiffer warnings on the drug, but was rebuked and excluded from safety meetings. More recenty, she was deposed as part of litigation over cardiovascular risks associated with the drug.........
read the rest of this story at http://bit.ly/b1Mgs8
Cheers CH
More updates on the subject
Do the Saudi's know something we don't know? 'Distribution of diabetes drug Avandia suspended in Kingdom' http://bit.ly/aT5iDz
U.S. group urges FDA to halt Glaxo's Avandia trial http://bit.ly/arV9x1 is this the final nail in rosglitazone's shelf life
Cheers CH
rosiglitazone no use in Alzheimers
Though I'd share this with readers Carl
The motto of drug companies should be
' if at first you dont succeed then try try again'.
Rosiglitazone Fails to Show Impact on APOE4-Stratified Patients With Alzheimer's Disease: Presented at ICAD
VIENNA, Austria -- July 14, 2009
Rosiglitazone shows no significant benefit in patients with mild to moderate Alzheimer's disease, according to an analysis of the secondary endpoints of a clinical trial presented here at the Alzheimer's Association 2009 International Conference on Alzheimer's Disease (ICAD).
http://www.docguide.com/news/content.nsf/news/852571020057CCF6852575F300...
I love the quote from one of their main scientist
"The main trial was also negative," said Claire Alderton, Neurological Studies, Neurosciences Medicines Development Center, GlaxoSmithKline, Greenford, Middlesex, United Kingdom, on July 12. "These results were very disappointing."
Basically, we wont be making money from this drug by trawling it around as many conditions as possible
Cheers Carl
keeing upto date with rosiglitazone news
Here is a neat site to keep up to date wtih breakingRoiglitazone news http://www.topix.com/drug/avandia
Cheer CH