Avandia: Tree in a Forest?

If a tree falls in a forest and no one is there to see it, does it make a sound?

If Avandia fails to recover from the recent media-hyped drug safety crisis, does it really matter?

I recently spoke with a physician-scientist who seemed to suggest that many people may be too quick to defend Avandia (rosiglitazone) given another alternative: Actos (pioglitazone). While there are relatively few studies comparing the two drugs, the small studies that are available so far suggest that Avandia increases LDL (low-density lipoproteins, the “bad cholesterol”) and HDL (high-density lipoproteins, the “good cholesterol”) while Actos decreases LDL and raises HDL. Ideally, one wants to lower LDL and raise HDL. Therefore, Actos improves a diabetic patient’s lipid profile, while Avandia seems to worsen it or not improve it. Considering that cardiovascular disease is the major long-term complication of diabetes mellitus, achieving and maintaining a good lipid profile is very important for long-term survival and reduction of disability/morbidity. The two drugs seem to be similarly effective at reducing blood sugar (glucose) levels and seem to have similar bioavailability. Overall, this would seem to suggest that pioglitazone (made by Takeda Pharmaceuticals) is a better drug for diabetics.

(To its credit, rosiglitazone does have a higher binding affinity to PPAR-gamma, its receptor, than does pioglitazone, but the clinical relevance of this finding is unknown.)

Interestingly, Steven Nissen, M.D. who published the NEJM study has conducted studies for Takeda Pharmaceuticals (as he declared in the article) through his Cleveland Clinic Cardiovascular Coordinating Center, but he claims to not receive any financial benefits from any pharmaceutical companies he consults for (it’s unclear whether or not he consults for Takeda). Given his track record, I’m willing to believe the latter statement, though he still may have some bias for Actos over Avandia. On the other hand, if one compares Actos and Avandia, can one blame him for his bias or assessment?

It would be nice to see GSK’s large Avandia trial completed, but it’s unclear whether it will weather the media hype over Nissen’s study (if patients drop out of the trial). Though this is a non-ideal situation, will it really matter in the end?

References:
Drug Digest
AccessMedicine

Note:
Neither the physician I spoke to nor I have any financial conflicts of interest or ties to either GlaxoSmithKline or Takeda.

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