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In Reply: Dr Najman and Dr Parra and colleagues raise important and valid concerns about dual PPAR agonists. Both letters recommend caution in the coadministration of fibric acid derivatives and thiazolidinediones, a strategy that would activate both PPAR- and receptors via 2 separate agents. Najman points out that some studies using the older PPAR- agents gemfibrozil and bezafibrate showed nonsignificant increases in mortality. In addition, the recent Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study showed a 19% higher mortality rate in the fenofibrate treatment group (P = .22).¹ In the muraglitazar analyses, we could not assess the impact of coadministration of the approved fibric acid derivatives because these agents were prohibited in the study designs.^2-3

Both letters suggest that morbidity and mortality trials are needed before approval of new therapeutic classes to be used in high-risk populations, such as patients with diabetes. I would disagree with such a . . . [Full Text of this Article]

Steven E. Nissen, MD
nissens@ccf.org
Department of Cardiovascular Medicine
Cleveland Clinic Foundation
Cleveland, Ohio

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