The rosiglitazone controversy: the Indian perspective.

In this era of evidence based medicine and drug discovery we are fortunate to get new molecules as treatment options but they are under continuous pharmacovigilance.The arrival of the thiazolidione compounds (also known as ‘glitazones’) with the introduction of troglitazone for treatment of type 2 diabetes heralded a new era in the management of type 2 diabetes. For the first time, a class of drugs to address the main pathophysiological defect in type 2 diabetes namely, impaired insulin action (or insulin resistance) had become available.1 Hardly had the euphoria regarding troglitazone settled with sales in excess of 2.1 billion dollars, when the drug had to be abruptly withdrawn following its hepatotoxic effects leading to 63 deaths in the United States.2 The introduction of the two subsequent drugs in this class namely rosiglitazone and pioglitazone was therefore viewed with great suspicion with the Food and Drug Administration (FDA) initially recommending mandatory liver function tests.3 It soon became apparent that these two classes of drugs were not hepatotoxic and liver function tests were soon declared unnecessary. However, they were not without side effects. Weight gain, pedal edema, a mild drop in haematocrit and fluid overload had been reported from studies abroad4 and from India.5 A slight increase in risk of cardiac failure has also been documented with both rosiglitazone6 and pioglitazone7 and these side effects appear to be a class effect. Meanwhile, there were also exciting positive developments. The ADOPT study showed that rosiglitazone scored over both Metformin and Glyburide (Glibenclamide) with respect to slowing down of monotherapy failure in newly diagnosed type 2 diabetic subjects.8 Going a step further, the “DREAM” study showed a 62% risk reduction in development of diabetes in subjects with pre-diabetes,6 albeit, the effect