We found rapid increases in glitazone use from their market debut until 2005. As scientific evidence, FDA advisories, and media coverage of their potential cardiovascular risks accrued, there was a sharp decline in rosiglitazone use; the initial decline began up to 2 years prior to the May 2007 FDA advisory. Despite a class-wide advisory in August 2007, pioglitazone treatment visits did not similarly decline. Consistent with settings of technology adoption (9
), decreases in rosiglitazone and pioglitazone use occurred nonselectively, rather than among those at highest cardiovascular risk (data not shown). These changes are important because glitazones were widely adopted into practice following their market debut, despite questions regarding their potential safety.
The substantial difference in market response to the FDA advisories between rosiglitazone and pioglitazone is noteworthy, and debates continue regarding the degree to which the cardiovascular risks that have been best demonstrated with rosiglitazone reflect a class-effect. Considerable evidence supports the greater safety of pioglitazone as compared with rosiglizatone (11
), and the fact that declines in rosiglitazone began far prior to the FDA advisory suggests that clinicians, to some degree, may have heeded early safety signals (2
). Nevertheless, the continuing uncertainty regarding the cardiovascular risks of these agents, as well as the degree of within-class heterogeneity in risk, suggests the importance of the routine inclusion of cardiovascular end points in studies that are used to seek FDA approval for diabetes therapies (13
). The potential risks of the glitazones, relative to other available agents (e.g., sulfonyureas, biguanides), also suggests their limited role as monotherapy for diabetes or use in patients at elevated risk of congestive heart failure or ischemic heart disease.
Our study has several limitations. We examined limited outcomes and used cross-sectional data precluding examining longitudinal prescribing patterns. Nevertheless, our findings suggest a substantial decrease in the use of rosiglitazone by these office-based physicians during the FDA advisories that occurred between February 2007 and May 2008. Similarly large reductions in pioglitazone were not observed, nor did reductions in glitazone use appear to be concentrated among the elderly or those otherwise at highest risk for adverse events from these therapies. The public health impact of the changes described is not clear.