Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes

Conclusion: Rosiglitazone is associated with an increase in myocardial infarction and risk of death from cardiovascular causes. Summary: Rosiglitazone was introduced in 1999 as oral treatment for type 2 diabetes. It is widely used as monotherapy or in fixed-dose combinations with either metformin or glimepirid. Rosiglitazone acts to lower blood sugar by increasing insulin sensitivity of peripheral tissues. Individual studies of rosiglitazone have confirmed its effect on reduction of blood sugar and improvement in glycosylated hemoglobin levels. Studies, however, were not powered to assess cardiovascular morbidity and mortality. In this article the authors reported results of a meta-analysis that included published literature, the Food and Drug Administration Web site, and a clinical trials registry maintained by GalxoSmithKline, the manufacturer of rosiglitazone. The analysis included studies that had a duration of >24 weeks, used a randomized control group, and provided outcome data for myocardial infarction and death from cardiovascular causes. Of 116 potentially relevant studies, only 42 met the inclusion criteria for the analysis. Focus was on tabulation of all occurrences of myocardial infarction and death from cardiovascular causes. A fixed-effect model was used to combine the data. In the 42 trials, the mean age of subjects was 56 years and the mean glycosylated hemoglobin level was 8.2%. The odds ratio for myocardial infarction in the rosiglitazone group compared with the control groups was 1.43 (95% confidence interval [CI], 1.03 to 1.98; P = .03). The odds ratio for death from cardiovascular causes in patients taking rosiglitazone versus controls was 1.64 (95% CI, 0.98 to 2.74; P = .06). Comment: The authors acknowledge in the discussion of the article that a few events either way may have influenced the results of this analysis. Nevertheless, there seems to be no particular benefit for rosiglitazone other than reducing laboratory measures of glycemic control. Rosiglitazone has no known favorable effect on microvascular disease or other complications of diabetes. Given the results of this study, there seems little rationale for continued use of rosiglitazone for treatment of type 2 diabetes.