Impact of rosiglitazone meta-analysis on use of glucose-lowering medications

BACKGROUND: In May 2007 Nissen and Wolski reported the results of a meta-analysis showing an association between use of rosiglitazone and increased risk of myocardial infarction (N Engl J Med 2007;356(24):2457–2471). Rosiglitazone is an insulin-sensitizing agent used to control blood glucose levels in patients with type 2 diabetes. Subsequent analyses provided evidence that the meta-analysis led to a decline in new and prevalent use of rosiglitazone. We sought to evaluate the impact of the meta-analysis on patterns of use of glucose-lowering drugs and patterns of initiation, cessation and switching of drug therapy, and to estimate these effects in relation to other predictors of initiation and cessation of rosiglitazone. METHODS: We used an interrupted time series analysis to test the impact of the meta-analysis on monthly utilization of glucose-lowering drugs for the 4.3 million residents of the province of British Columbia. We used multivariate logistic regression with generalized estimating equations to test predictors of initiation and cessation of rosiglitazone, including the influence of microvascular and macrovascular comorbidities, before and after the meta-analysis. RESULTS: A comparison of predicted and observed utilization for November 2007 showed that use of rosiglitazone declined by 40% (95% confidence interval 39%–42%), whereas use of pioglitazone, insulin and sulfonylureas increased. The presence of macrovascular comorbidities strengthened both the negative impact of the meta-analysis on initiation of rosiglitazone therapy and the positive impact of the meta-analysis on cessation of this drug. INTERPRETATION: The shift in utilization from rosiglitazone to insulin and sulfonylureas and the modest increase in use of pioglitazone suggest that the latter drug was not embraced as a less harmful alternative to rosiglitazone. Macrovascular comorbidities played a greater role in decisions to start or stop rosiglitazone therapy after the meta-analysis was published.