Is rosiglitazone really more toxic than pioglitazone?
Since the initial reports published in the New England Journal of Medicine numerous research articles and press reports claim that rosiglitazone (R) is more toxic than pioglitazone (P) without relating toxicity to the dose of the drug. In reality, these chemically closely related compounds have most probably similar efficacy and toxicity, although they differ in relative potency. The problem is that R was studied and clinically used at relatively high doses in relation to its efficacy. The highest dose of R (but not of P) is likely to be too high for safe clinical use. The selectioin of the clinical doses for R was unfortunate. The highest dose of R is probably already maximal or even supramaximal in relation to its efficacy, while that of P is submaximal. At the highest dose (8 mg) R can be expected to be more toxic than P at the highest (but still submaximal) dose. If used at doses below those producing maximal efficacy R is not likely to produce more cardiovascular toxicity than P. This means that R is likely to be safe and probably as effective as P at doses lower than recommended. Instead of removing the drug, FDA should have insisted on its evaluation at lower doses. Also, it is logical to expect that P will have the same cardiovascular toxicity as R, if used at doses higher than recommended.