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When Rezulin was removed from the market several years ago, the top endocrinologist I worked with was quite upset. Of course he knew about the few cases of severe liver failure and the rare death, but he also knew how many patients benefited directly from the drug. “Avandia will be next,” he predicted.

Thiazolidinediones (TZDs) are a class of drugs which improve insulin receptor sensitivity and reverse the insulin resistance typically seen in type 2 diabetes. Since most type 2 diabetics have too few receptors per body surface area, the TZDs are very useful drugs.

The fact that patients on the remaining two TZDs (Avandia and Actos) can gain weight on these drugs is not news. The question of whether they can cause or worsen heart failure has long been discussed.  Unfortunately the current raging debate and targeting of the FDA and the drug manufacturers doesn’t directly address this question. The existing information is based on mathematical analyses of previously published data and is weak.

Prospective randomized trials are necessary, but what should a clinician do? All too often, as the pendulum swings from panacea to panic, a perfectly good medication has its reputation damaged or destroyed based on limited or overblown results, all in the name of drug safety.

To give just one example as it relates to TZDs, it is clear that controlling blood sugar is important in preventing diabetic end organ damage. Among these crucial organs we try to protect is the heart. Everyone agrees that Avandia and Actos help to significantly lower blood sugar. But as their reputations damaged in the media, how many safety-driven zealots have stopped to consider what uncontrolled sugars will mean to the heart? Now that patients— and doctors—will be running from drugs with “black box” warnings, what will be the clinical results? In other words, which will cause more heart failure: the drugs themselves, or stopping them?

