The first question is clinical: what are the benefits and harms of rosiglitazone as a treatment of Type 2 diabetes, and therefore for which patients under what circumstances should this drug be used?
The second question is about policy: what barriers, if any, have prevented physicians and patients from getting the best possible answer to the first question, and what can be done about them?
My take is that the first question is complex, and must be answered in light of what we know about all the other available options for type 2 diabetes. The meta-analysis has its problems and must be considered hypothesis generating. As I posted here there seem to be disparate effects on macrovascular disease between the two available TZDs, pioglitazone (Actose) and rosiglitazone (Avandia) which have a plausible basis due to differing effects on lipids and differing molecular mechanisms.
So how can we summarize and compare macrovascular outcomes associated with various treatments for DM-2?
Pioglitazone, the only TZD available other than rosiglitazone appears to reduce macrovascular events.
In the UKPDS metformin decreased stroke and all cause mortality in obese patients, but the overall results for metformin were not internally consistent.
Insulin therapy has not been demonstrated to halt macrovascular disease. There is evidence that intensive insulin treatment may in fact be associated with increased macrovascular disease but this is controversial.
The first generation sulfonylurea tolbutamide is associated with a marked increase in cardiovascular mortality in the UGDP trial. Other sulfonylureas carry the cardiovascular warning although they have not been similarly studied.
The clinical bottom line of all these findings is that macrovascular disease is an elusive target in DM-2 and choices of agents at this time must be governed by limited information.
Concerning the second question, barriers on both sides have prevented physicians and patients from getting the best possible answer regarding Avandia. GSK may have suppressed information and its defenders appear to have engaged in personal attacks on the lead author of the NEJM meta-analysis. On the other hand, the timing and manner of the release of the NEJM meta-analysis suggest a case of orchestrated hype.
Both sides have explaining to do. Although Dr. Nissen’s testimony in the Waxman hearing seemed evasive, he was frequently interrupted and not given a chance to elaborate on his answers. He should have the opportunity to convince us that the meta-analysis was not agenda driven.