Rosiglitazone- is it curtains down?

Rosiglitazone has become a hot topic for debate recently due to its consistent association with Cardiovascular events in patients with diabetes who are on this medication.

These agents(rosi & pioglitazone) increase insulin sensitivity, enhance glucose control, suppress inflammatory and cardiovascular risk markers, reduce proinflammatory cytokines, and improve vascular structure and function.

This issue started with the DREAM study presented in 42nd EASD meeting in Copenhagen in 2006 which included 5000 pts with prediabetes (& no CVS disease) ,showed a 62% reduction in incidence of diabetes over 3 yrs compared to placebo. But a letter to editor from Dr.Nissen brought out that rosiglitazone resulted in a 37% increase in adverse cardiovascular events, a finding that very nearly reached conventional levels of significance.

on May 21, 2007, the US Food and Drug Administration (FDA) published a “safety alert”, concluding that “serious concern” existed over GSK's rosiglitazone.

Subsequently two metaanlysis done on same topic ( Nissen et al in 2007, and FDA analysis in 2007 ) revealed a 30-40% greater risk of MI and a borderline-significant increased risk of death from cardiovascular causes. Many other studies showed nearly same risk with Rosiglitazone.So,on July 14,2010 FDA advisory comittee voted on this. It was a 20 - 12 to keep the drug on market, but with strong warnings.

Rosi's sister drug! Pioglitazone does not share this risk.And in fact it provides some cardiovascular benefit (PROactive trial -2005). Relative to rosiglitazone, pioglitazone improves triglycerides, HDL-C, non-HDL-C, and LDL particle concentration and size, although both agents increase LDL levels.

Both of them activate peroxisome proliferator-activated receptor (PPAR)α. But Pio acts on a different ligand than rosi, and thats probably why,the difference in their action.So for now, if we have to choose a TZD ,Pioglitazone seems a better option. Any questions?!