What will history say about the thiazolidinedione class of diabetes drugs like Avandia and Actos?

Every time I hear another piece of bad news about rosiglitazone (Avandia) or pioglitazone (Actos) I feel as though I am watching another piece of diseased flesh falling off a bloated and dying giant.  The thiazolidinediones (or TZDs or glitazones) was the juggernaut new "blockbuster" diabetes drug class of the past ten years.  Despite having no research studies showing long term benefit these drugs were pushed very persuasively onto the market.  But as I have detailed in previous posts the longer we looked the longer the list of problems and side effects grew while the evidence of meaningful benefit remained elusive.

http://gomeworld.typepad.com/morediabetesanswers/2010/06/why-would-you-ever-want-to-use-avandia-or-even-actos.html

This weeks brings more bad news.  The FDA has issued a warning that pioglitazone (Actos) may cause an increased risk of bladder cancer, especially with prolonged use of the drug.  We already know that the risk of developing bone-thinning (osteoporosis) with these drugs gets worse the longer you stay on them.

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm226257.htm

Another announcement today states that rosiglitazone (Avandia) is being taken off the market in Europe because of the likely increased risk of heart attacks, strokes and deaths associated with taking Avandia.  Avandia will, of course, still be available in the USA market.  Although sales in the USA are dropping Avandia still brings in annual revenue of over a billion dollars.

http://link.email.washingtonpost.com/r/BZYGW4/A7M5IB/30Y38H/VMINCB/Q0A68/E4/h

Why is it that the USA seems so much slower to act as Europe just did?  This is eerily reminiscent of the situation back in 1997 when troglitazone (Rezulin), the first drug in this class, was taken off the market in the UK with most of Europe quickly following suit, but was left on the US market for another full two years before the rising toll of deaths from liver failure convinced the FDA to remove it.  I wonder how long we will need to wait before we see the last of Avandia in the USA.

I do not write this with pleasure or malice.  I have nothing against pharmaceutical companies that work to develop new treatments that might benefit people with diabetes.  Far from it.  I applaud their efforts.  In the past few decades some other classes of drugs (like ACE-inhibitors and statins) have been proven over time to be dramatically beneficial for people with diabetes.  What concerns me is how easily fooled many doctors and patients are, and how readily we all want to believe the early hype about new drugs.  How impatient we all are.  We are rarely willing to do the rigorous long-term trials that can truly prevent us from allowing millions of people to be exposed for years to drugs that cause more harm than good.

Comments

[TheWriteScot]

What will history say about the thiazolidinedione class of diabetes drugs like Avandia and Actos?

[knowledge closet]

I recently came across your blog and have been reading along. I thought I would leave my first comment. I don't know what to say except that I have enjoyed reading your post and read the comments. Really a nice post here!

[knowledge closet]

Most of my family are diabetic and I feel likely to be one.. How could I avoid not passing this hereditary thing to my kids?

[buy neurontin]

Every time I hear another piece of bad news about rosiglitazone (Avandia) or pioglitazone (Actos) I feel as though I am watching another piece of diseased flesh falling off a bloated and dying giant. The thiazolidinediones (or TZDs or glitazones)...

[Carol]

For any medication, I believe there is always a side-effect. I think that is the consequence for altering how nature works. I hope we get to perfect science in the future - where there is only cure without any side-effects.

[David K. McCulloch]

Yes, Carol, there are side effects with all drugs. My Therapeutics and Pharmacology professor at Edinburgh University back in the 1970s referred to drug side effects as the "thorns on the therapeutic rose!" It is a great metaphor. As an avid gardener I have noticed that some of my most favorite roses with exquisite flowers and smell have the most wicked sharp thorns on their stems. With new drugs the tension is that people often want the potential benefit so-o-o-o badly that they want to rush the new drug through the FDA process and get it on the market as soon as possible. But often it takes 5-10 years or more of experience using a drug with large numbers of people before it becomes clear whether it casues more net good or net harm.