Thiazolidinediones and cardiovascular events in patients with type 2 diabetes mellitus: a retrospective cohort study of over 473,000 patients using the National Health Insurance database in Taiwan.
OBJECTIVE
Concern has been expressed over the cardiovascular risks associated with rosiglitazone and pioglitazone. This study investigates the association between oral antihyperglycaemics (rosiglitazone, pioglitazone, sulfonylureas and metformin) with myocardial infarction, congestive heart failure, angina pectoris, stroke and transient ischaemic attack.


METHODS
We used Taiwan's 2000-5 National Health Insurance database to conduct a population-based, retrospective cohort study of 473 483 newly diagnosed patients with type 2 diabetes mellitus. We classified study patients into five basic groups based on the agents they were prescribed during the study period: (i) rosiglitazone monotherapy; (ii) pioglitazone monotherapy; (iii) sulfonylurea-based therapy; (iv) metformin-based therapy; and (v) sulfonylurea and metformin-based therapy. Cox proportional hazards models were used to evaluate the association between the use of rosiglitazone or pioglitazone and the occurrence of cardiovascular events.


RESULTS
Patients receiving rosiglitazone monotherapy were at higher risk for any cardiovascular event (hazard ratio [HR] 1.89; 95% CI 1.57, 2.28), myocardial infarction (HR 2.09; 95% CI 1.36, 3.24), angina pectoris (HR 1.79; 95% CI 1.39, 2.30) and transient ischaemic attack (HR 2.57; 95% CI 1.33, 4.96) than those receiving metformin monotherapy. Overall, add-on rosiglitazone and pioglitazone were associated with comparable cardiovascular risk. Based on our point estimates, pioglitazone as an add-on therapy was found to have a favourable, but nonsignificant, effect on outcome.


CONCLUSIONS
Our findings extend the evidence from current literature to a real-world setting and support data from clinical trials that the disadvantages or harm caused by thiazolidinediones, especially rosiglitazone, may outweigh their benefits in patients with type 2 diabetes.
Hsiao
Fei-Yuan
FY
Institute of Health and Welfare Policy/Center for Health and Welfare Policy Research, National Yang-Ming University, Taipei, Taiwan.
Huang
Weng-Foung
WF
Wen
Yu-Wen
YW
Chen
Pei-Fen
PF
Kuo
Ken N
KN
Tsai
Yi-Wen
YW
D000368:Aged; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology; D015331:Cohort Studies; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D000077205:Pioglitazone; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D000077154:Rosiglitazone; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use; D013624:Taiwan / Q000453:epidemiology; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin; D000077205:Pioglitazone