Relationship between thiazolidinedione use and cardiovascular outcomes and all-cause mortality among patients with diabetes: a time-updated propensity analysis


  • Zeina A. Habib and Leonidas Tzogias made an equal contribution to the manuscript.



To investigate the association of the thiazolidinediones (TZDs), rosiglitazone, and pioglitazone, together and individually on the risk of cardiovascular outcomes and all-cause mortality, using time-updated propensity score adjusted analysis.


We conducted a retrospective cohort study in a large vertically integrated health system in southeast Michigan. Cohort inclusion criteria included adult patients with diabetes treated with oral medications and followed longitudinally within the health system between 1 January 2000 and 1 December 2006. The primary outcome was fatal and non-fatal acute myocardial infarction (AMI). Secondary outcomes included hospitalizations for congestive heart failure (CHF), fatal, and non-fatal cerebrovascular accidents (CVA) and transient ischemic attacks (TIA), combined coronary heart disease (CHD) events, and all-cause mortality.


19 171 patients were included in this study. Use of TZDs (adjusted hazard ratio (aHR) with propensity adjustment (PA), 0.92; 95% confidence interval (CI) 0.73–1.17), rosiglitazone (aHR with PA, 1.06; 95%CI 0.66–1.70), and pioglitazone (aHR with PA, 0.91; 95%CI 0.69–1.21) was not associated with a higher risk of AMI. However, pioglitazone use was associated with a reduction in all-cause mortality (aHR with PA, 0.60; 95%CI 0.42–0.96). Compared with rosiglitazone, pioglitazone use was associated with a lower risk of all outcomes assessed, particularly CHF (p = 0.013) and combined CHD events (p = 0.048).


Our findings suggest that pioglitazone may have a more favorable risk profile when compared to rosiglitazone, arguing against a singular effect for TZDs on cardiovascular outcomes. Copyright © 2009 John Wiley & Sons, Ltd.