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Adverse cardiovascular events during treatment with pioglitazone and rosiglitazone: population based cohort study

BMJ 2009; 339 doi: (Published 19 August 2009) Cite this as: BMJ 2009;339:b2942
  1. David N Juurlink, division head12345,
  2. Tara Gomes, epidemiologist5,
  3. Lorraine L Lipscombe, assistant professor56,
  4. Peter C Austin, senior scientist457,
  5. Janet E Hux, senior scientist1245,
  6. Muhammad M Mamdani, centre director2458
  1. 1Division of Clinical Pharmacology and Toxicology, Department of Medicine, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, Canada M4N 3M5
  2. 2Department of Medicine, University of Toronto
  3. 3Department of Pediatrics, University of Toronto
  4. 4Department of Health Policy, Management, and Evaluation, University of Toronto
  5. 5Institute for Clinical Evaluative Sciences, Toronto
  6. 6Women’s College Hospital, Toronto
  7. 7Department of Public Health Sciences, University of Toronto
  8. 8Applied Health Research Centre, Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto
  1. Correspondence to: D Juurlink dnj{at}
  • Accepted 15 May 2009


Objective To compare the risk of acute myocardial infarction, heart failure, and death in patients with type 2 diabetes treated with rosiglitazone and pioglitazone.

Design Retrospective cohort study.

Setting Ontario, Canada.

Participants Outpatients aged 66 years and older who were started on rosiglitazone or pioglitazone between 1 April 2002 and 31 March 2008.

Main outcome measure Composite of death or hospital admission for either acute myocardial infarction or heart failure. In a secondary analysis, each outcome was also examined individually.

Results 39 736 patients who started on either pioglitazone or rosiglitazone were identified. During the six year study period, the composite outcome was reached in 895 (5.3%) of patients taking pioglitazone and 1563 (6.9%) of patients taking rosiglitazone. After extensive adjustment for demographic and clinical factors and drug doses, pioglitazone treated patients had a lower risk of developing the primary outcome than did patients treated with rosiglitazone (adjusted hazard ratio 0.83, 95% confidence interval 0.76 to 0.90). Secondary analyses revealed a lower risk of death (adjusted hazard ratio 0.86, 0.75 to 0.98) and heart failure (0.77, 0.69 to 0.87) with pioglitazone but no significant difference in the risk of acute myocardial infarction (0.95, 0.81 to 1.11). One additional composite outcome would be predicted to occur annually for every 93 patients treated with rosiglitazone rather than pioglitazone.

Conclusions Among older patients with diabetes, pioglitazone is associated with a significantly lower risk of heart failure and death than is rosiglitazone. Given that rosiglitazone lacks a distinct clinical advantage over pioglitazone, continued use of rosiglitazone may not be justified.


  • We thank Baiju Shah and Donald Redelmeier for comments on an earlier draft of this manuscript and Ashif Kachra for assistance with preparing the manuscript.

  • Contributors: All authors contributed to the conception and design of the study. TG collected the data, and all authors contributed to the analysis and interpretation. DNJ drafted the article; all authors revised it critically for important intellectual content and approved the final version submitted for publication. DNJ is the guarantor.

  • Funding: This project was supported by a grant from the Ontario Ministry of Health and Long Term Care, which had no role in the design, analysis, writing, or interpretation of the study. DNJ is supported by a new investigator award from the Canadian Institutes for Health Research. PCA is supported by a career investigator award from the Heart and Stroke Foundation of Ontario. LLL is supported by a clinician scientist award from the Canadian Diabetes Association and Canadian Institutes for Health Research.

  • Competing interests: None declared.

  • Ethical approval: The research ethics board of Sunnybrook Health Sciences Centre approved the study.

  • The opinions, results, and conclusions are those of the authors, and no endorsement by Ontario’s Ministry of Health and Long-term Care or by the Institute for Clinical Evaluative Sciences is intended or should be inferred.

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