July 28, 2010

Rosiglitazone and the Case for Safety Over Certainty

Author Affiliations

Author Affiliations: Sunnybrook Research Institute; Departments of Medicine, Pediatrics, and Health Policy, Management, and Evaluation, University of Toronto; and Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.

JAMA. 2010;304(4):469-471. doi:10.1001/jama.2010.954

Approximately 10 years ago, the thiazolidinediones rosiglitazone and pioglitazone were introduced for the treatment of type 2 diabetes. Like their forerunner troglitazone, which was removed from the market following reports of hepatotoxicity, these drugs act on the gamma subtype of peroxisome proliferator-activated receptors (PPAR-γ) in the cell nucleus, resulting in heightened insulin sensitivity and improved glycemic control.1 Because insulin resistance is a common feature of type 2 diabetes, the biological effects of thiazolidinediones made these drugs appealing to patients with diabetes and to their physicians who were looking for yet another way to avoid the need for insulin. Within a few years, both drugs became multibillion-dollar products despite no direct evidence that they actually prevented the complications of diabetes.

First Page Preview View Large
First page PDF preview
First page PDF preview