Endocrinology: April 2010 Archives

From heartwire: Reported ambivalence about enrolling patients in the TIDE trial, a head-to-head study of rosiglitazone (Avandia; GSK) and pioglitazone (Actos; Takeda) in patients with type 2 diabetes, endangers the assessment of vitamin D supplementation.

That's because the GSK-funded and FDA-commissioned trial uses a 2-by-2 factorial design to answer 2 questions.

• Does long-term treatment with rosiglitazone or pioglitazone reduce the risk of vascular events?
• Does even longer-term treatment with vitamin D reduce the risk of death or serious cancer?

Quoted by heartwire, US principal investigator Jeffrey Probstfield said, "...I can tell you that probably at least half of the investigators in the US who signed up to do this [trial] find the vitamin D question more compelling and interesting than the rosiglitazone-vs-pioglitazone-vs-placebo issue."

If the trial is sidelined over enrollment problems (because of the controversy about rosiglitazone's safety), GSK is unlikely to support a trial assessing only vitamin D, Probstfield reasonably concluded.

A search of the NIH database reveals that, while there are several other studies assessing the possible health benefits of vitamin D, TIDE is the only trial examining the supplement's death- or cancer-preventing potential.

TIDE = Thiazolidinedione Intervention With Vitamin D Evaluation.

(With apologies for "Repurposing.")

Largely because of a controversial 2007 meta-analysis by the controversial and controversy-stirring Steve Nissen, sales of the antidiabetic drug Avandia (rosiglitazone) dropped more than 50%, from about $3 billion in 2006 to $1.2 billion in 2009. As an apparent consequence, the drug's manufacturer, GlaxoSmithKline, has been searching for an alternative indication for the product, especially given that the drug is at risk of being pulled from the market. In addition, the use patent for Avandia in type 2 diabetes (the drug's primary indication) expires in 2 years.

Unfortunately for GSK and people with Alzheimer disease, trials of an extended-release version of the drug (the REFLECT studies) failed to show any cognitive benefits with Avandia when added to or compared with the standard treatment of donepezil (Aricept; Pfizer) or placebo. Last year, GSK announced that it was abandoning its development of Avandia for AD.

But plenty of other GSK-sponsored and non-GSK trials of Avandia have been conducted or are ongoing. These include studies in asthmatic smokers,* ulcerative colitis,* HIV-related lipoatrophy, and chronic kidney disease. Avandia's effects on preventing or treating certain types of solid tumors also have been or are under investigation.

* In addition to mitigating insulin resistance, Avandia appears to have anti-inflammatory properties.