Diabetes Drug Tied To Heart Risk In Study

Analysis Reveals Avandia Linked To 43 Percent Increased Risk For Heart Attack And Possibly Death

(CBS/AP)  Avandia, the biggest-selling diabetes drug in the world, is linked to a greater risk of heart attack and possibly death, says a new scientific analysis published online Monday.

More than 6 million people worldwide have taken the drug sold by London-based GlaxoSmithKline PLC since it came on the market eight years ago. Pooled results of dozens of studies revealed a 43 percent higher risk of heart attack and a 64 percent greater risk of cardiovascular death, according to the review published by the New England Journal of Medicine.

Experts said the overall risk was small and cautioned people not to stop taking the drug on their own but to talk to their doctors.

"There are more heart attacks, more strokes, deaths, et cetera," one of the study's researchers, Dr. Steven Nissen, said. "It is most urgent that both the FDA and the company look at the original source data and do careful analysis."

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Only On The Web: Study author Dr. Steven Nissen discusses the link between Avandia and increased risk of heart attack and cardiovascular death.

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The company downplayed the report of heart risks, saying the analysis by Dr. Nissen and statistician Kathy Wolski at the Cleveland Clinic is not definitive scientific proof. In a conference call Monday, Dr. Lawson McCartney, who leads Glaxo's diabetes drug development, said the company is not seeing "anything like" the problems reported in the medical journal.

"We remain very confident in the safety and of course in the efficacy of Avandia as an important diabetic medicine," McCartney said.

GlaxoSmithKline earns $3 billion a year from the drug, the biggest-selling diabetes drug in the world, according to Forbes magazine.

The government will take no immediate action on a label change or other measures regarding the drug, said Dr. Robert J. Meyer of the U.S. Food and Drug Administration's Center for Drug Evaluation and Research.

FDA officials acknowledged that Glaxo submitted information last August indicating some increased risk from the drug but that other studies were contradictory.

CBS News correspondent Wyatt Andrews reports the FDA said it has studied the same data as Nissen, but that "unpublished data" suggests "contradictory evidence about (Avandia's) risks" — which essentially means the FDA doesn't have enough evidence to pull the drug off the market.

However, several members of Congress expressed alarm at the report and said they would hold hearings on the safety issues.

Avandia is used to treat Type 2 diabetes, the most common form of the disease, which is linked to obesity and afflicts 18 million Americans and 200 million people worldwide. This form of diabetes occurs when the body does not make enough insulin or cannot effectively use what it manages to produce. Avandia helps sensitize the body to insulin and was considered a breakthrough medication for blood-sugar control.

In a strongly worded editorial accompanying the study, patients were warned not to quit Avandia on their own without discussing their concerns with their doctors, wrote Drs. Bruce Psaty and Curt Furberg. To the extent that the new analysis shows valid risks, the drug "represents a major failure of the drug-use and drug-approval processes in the United States," they said.

Psaty, a researcher at the University of Washington, said the Nissen study means there's no good reason for most patients to take Avandia.

"There is little evidence for using this drug," Psaty told WebMD. "The purpose of reducing blood sugar is to prevent cardiovascular events. Now the possibility of cardiovascular benefit associated with Avandia appears remote — indeed, it appears linked to harm. So the rationale for prescribing it at this time is just not clear."

When the drug was approved, "evidence was at best mixed" on its benefit, wrote the two doctors. Both have been frequent critics of the FDA's failure to spot dangers in the drug approval process and its conduct in the case involving Vioxx. The popular arthritis medicine sold by Merck & Co. was taken off the market in 2004 when heart problems came to light after it had been taken by millions of people

Several experts said Avandia was another example of the FDA failing to detect a safety problem early enough.

"This study is sure to increase criticism of the U.S. Food and Drug Administration for approving Avandia in the first place," said CBS News correspondent Barry Bagnato.

The report on the diabetes drug's risks follow Glaxo's $2.5 million settlement of a lawsuit filed by former New York Attorney General Eliot Spitzer over the release of data on the safety and effectiveness of its drugs. Spitzer, now New York governor, accused Glaxo of fraudulently withholding some results of studies that had examined the safety of prescribing the antidepressant Paxil to children.

GlaxoSmithKline disputed that it attempted to mislead anyone, and said it has always been in favor of widespread disclosure of clinical trial results.

The company's clinical trials registry (http://ctr.gsk.co.uk) is available to the public, although the reports within it are highly technical and may appear incomprehensible to an untrained reader.

In a study published last September, the drug rosiglitazone (Avandia) appeared to cut the risk of developing diabetes or dying by more than half. It also helped restore normal blood-sugar function in many participants. That study involved about 5,000 people with "pre-diabetes," or blood-sugar abnormalities.

But even that study's researchers acknowledged that a small percentage of those on Avandia developed heart failure.

[reel-crazy]

Clinical studies by the FDA prior to it's approval and release should have revealed this problem. Large companies, like GSK but not exclusively, have the power to get these drugs on the market fast because their only concern is profit. Thats why they leave all these disclaimers so vague in their advertisements. Check out their website at www.avandia.com and look at how happy these people are on their front page, but it's amazing that I don't see one mention of this problem there. Imagine that.....

[salvo19]

This drug business is over and over like Vioxx,
Celebrex, etc. i sincerely thing the FDA is in
cahoots with the drug companies. If FDA cannot
do their job then reorganize it and replace the
present staff for being so incompetent.

[sentry88]

Thank you Dr Phillips for taking me off of this drug.

[rebelrose62]

I started taking Avandia 4 years ago. About 2 years later My heart started beating hard alot. My feet and legs started swelling, Then I saw a commercial on TV about this medication. Near the end of the commercial it gave the risks. And what they had said was the same problems I started having. Well anyway, I went to see my Doctor and told her my concerns about the medication and told I didnt want to take it anymore. She took me off of it and the problems I was having were no longer a problem. I am happy to say that I am now using the Novolog flexpen and I am very happy with that.

[lebrecht-2009]

What about ACTOS?
This is a similar drug. Has any more research been done and is this drug also the same risk factor?

Of course the other alternative is to take insulin. I was on insulin for over 15 years and my new endocrinologist has taken me off it and put me on a combination of Actos and Metformin.

ONE has to wonder at how much is done from the push of the pharmaceutical companies and how much actual proof there is as to which and what is the
safest and best medication with the least risk. The only risk as far as I know from Insulin is the lows. If a patient is vigilant about testing often that risk is far less than any claims otherwise.

One has to wonder.
Anne

[heartlight3]

It sure seems as though there are a lot of drugs lately that have been approved by the FDA that end up being recalled. This indicates that the FDA is not doing it's job. The purpose of the FDA is not to promote new drugs for the Pharmaceutical companies, but to protect us from drugs which are not safe. I would hate to think that the FDA is as crooked and incompetent as other institutions in our government. At the very least they should require longer and more thorough testing.

[dawalden2005]

My Doctors took me off Avandia 2 weeks ago, after I became very very sick. My liver enzymes which were normal before starting the medication became 6 times the normal value. I had alot of swelling, nausea, vomiting. After being off the medication for 2 weeks my liver enzymes are now only slightly elevated and I feel almost back to normal.

[drinuk]

I have repeatedly warned that the incestuous and financial relationship between government, the politicians and the FDA with the pharmaceuticals is nothing short of genocide.
All political donations from Big Pharma should be stopped Now! Any politician national, state or even local who holds stock in Big Pharma should be fired and fined. Employee's of whatever status in the health or health insurance industry should also be banned from holding Big Pharma stocks. The financial and corrupt gateway in which dangerous drugs become approved must be closed and new laws enacted to keep it closed, punishment for offending should be simple, clear and severe, 25 years with no remission for any collusion. Enough is Enough, the people have to get this problem sorted because as sure as hell the politicians will never do it, they are up to their necks in the scam.

[drinuk]

AND Seandgreen. So the US as no Regulatory powers with regard to herbs ! Now you are either a nieve idiot or you work in the crooked health industry. At Big Pharma's request the FDA have banned several natural cancer cures, WHY because they cannot obtain a patent on them and were ably supported by crooked politicians and the FDA. Wake Up Bone Head, J Edgar Hoover said that the corruption was so great that ordinary folks could not comprehend it or refused to believe it, well! you proved him right.

[drinuk]

Seandgreen, You also suggest that Big Pharma has bought us out of the jungle, if that is so why is Cancer up by over 20% and Chemo only 10% effective ? Good business to be involved in but not so good if you are a sufferer.
Let us look at ASPARTAME, invented by accident as a bi product, found to be Sweet, 30 times sweeter than sugar and a fraction of the price, refused approval in 1982 by the FDA but after achieving political office Serles CEO had a word in the ear of the FDA and lo' and behold it got approval. NOW proven by independent Italian research to cause tumours. Where would we be without Big Pharma ? A dammed sight healthier than we are now. They have turned cancer into a very profitable industry by failure and corruption. AND I could go on.....AIDS ????

[alphaa10-2009]

Count on the corporate PR flaks-- pardon-- "spokespersons" at Glaxo to deny everything.

This study is a glowing tribute to the Cleveland Clinic, but unfortunately, credit cannot go to the FDA, as well.

The FDA, "the people's watchdog", became an industry lapdog long ago. Standard operating procedure at FDA is to hire regulatory staff from the ranks of the pharmaceuticals-- or from their covey of subsidized researchers.

As a direct result, the FDA has little scientific or professional credibility left. The current FDA blessing for Avandia is another case in point.

[grazinggoat]

CBS: 'GlaxoSmithKline earns $3 billion a year from the drug, the biggest-selling diabetes drug in the world, according to Forbes magazine.'

-GSK will fight all accusations in order to keep this drug on the pharmacy shelves. It represents almost 10-15% of it sales, that also represents a fatty cow for the company, a patent-protected drug until a relatively long period before it can be copied (generics) .

- Now the task would be if this drug increased the lethal side effects by cardiovascular death, higher than the benefits it gives to the patients. If survivals over dying diabetics overcome the deaths from the side effects, well rosiglitazone (Avendia) should be kept in the pharmacopae.

- A diabetes-mellitus classes of medication should be tested in order to conclude to the lowest incidence on lethat side effects.

-GSK is particularly inclined on denying the side effects (and overlooking them). It was the case with Paxil, an antidepressant that GSK intended to market prescribing to kids. What greed can drive a company into nearly unethical practices, in order to make more money? Especially when the sales and marketing departments pressure the ethical staff into a delicate position in such a way that they are put in a conflicting position driving the writing the marketing expenses to medical PRESCRIBERS as part of research and Development, oftenly wrongly bulging the research and real developments are limitied to less than half of what is claimed.

[grazinggoat]

- We gotta be careful before we judge the FDA. In many cases, it's been shown after years of usage, a drug shows some side effects, that are deleterous to humans more than beneficial, but being so scarce that only long time usage will tell.

[monied-2009]

Unfortunately, this is not a "new" problem!

A quick internet search on the topic of Avandia and warnings brought up a letter written to the GlaxoSmithKline from the FDA back in July 2001:

http://www.pharmcast.com/WarningLetters/Yr2001/July2001/Glaxo0701.htm
"These revisions to the PI included a new warning regarding cardiac failure and other cardiac effects"

This letter certainly shows that the FDA was aware of the possible adverse heart conditions (among other problems) that Avandia could bring about.

Why is it that 6 years later, we still do not have appropriate drug trials showing the full effects of this drug? And why is it that the FDA and the drug company both are denying that they were aware of problems?

[alphaa10-2009]

monied said, "Why is it that 6 years later, we still do not have appropriate drug trials showing the full effects of this drug? And why is it that the FDA and the drug company both are denying that they were aware of problems? ...
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The FDA has a classic pattern of choosing review panelists friendly to the drug makers. This is the principal mechanism by which the FDA routinely sells its integrity to the pharamceutical industry.

On other occasions, however, certain annoying clusters of evidence must be tidied up and/or ignored. Often enough, this leaves a trail of bias and deception clearly traceable back to the FDA.

Amazingly, if we thought there might be some connection between what Big Pharma wants and what Big Pharma gets, we would be right in almost every case.

Who might have missed the recent scandal in which a temporary FDA chief was admonished for lax professional behavior? That is, regulating a drug in which he had a personal financial interest-- only to draw attention to the fact the guy was also a veterinarian, by training! (Another Bush political appointee-- heckuva job!)

(Hmmmm. If an animal doctor is good enough for the rest of America, is the Bush personal physician a needless luxury? Put another way, how much care does Bush really need? Especially, now? 8 )

[drinuk]

Seandgreen, Go to www4.dr-rath-foundation.org have a good read, interested to hear your learned opinion. Perhaps you would give us your opinion on Laetrile, and Bitter Melon, why the Japanese Pharmaceuticals have invested millions trying to "Break It Down" into a patentable product, only to find it is succesful against cancer in it's natural state and unpatentable, my guess is that it too will be soon banned and for that reason alone.

A few months ago on this very website it was stated that a joint Australian and American study
had found that whilst cancer rates had increased by 20% Chemo had proved to be effective in only 10% of cases, I was quoting CBS.

With regard to your comments that we all enjoy a more healthy and longer life, Could that be due more to better hygiene, refrigeration and improved lifestyle. Prior to 1940 there was a marked decrease in infectious disease, hardly due to Big Pharma but clean running water, improved working conditions and better diet.

With the greatest respect, To Thine Own Self Be True". At the outset of every day do you honestly recall the words "First Do No Harm" ?

[drinuk]

seandgreen, Last word Sir ! it is blatantly obvious where you are coming from and I note as will others the lack of comment on several other points raised. The subjects to which I expected a response you conveniently ducked and dived from. Now get back to your patients as they need you more than I do. Goodnight.

[incog-nito]

Moral of the story: If you want to reduce the risk of a heart attack, DO NOT get diabetes!

[retiredinmex]

I live in Mexico with Type 2 Diabetes. Does Avandia have any other names...I want to make sure I'm not taking it now.