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Benefits and harms of antidiabetic agents in patients with diabetes and heart failure: systematic review

BMJ 2007; 335 doi: (Published 06 September 2007) Cite this as: BMJ 2007;335:497
  1. Dean T Eurich, research associate1,
  2. Finlay A McAlister, associate professor2,
  3. David F Blackburn, assistant professor3,
  4. Sumit R Majumdar, associate professor2,
  5. Ross T Tsuyuki, professor4,
  6. Janice Varney, librarian1,
  7. Jeffrey A Johnson, professor5
  1. 1Institute of Health Economics, Edmonton, AB, Canada, T5J 3N4
  2. 2Division of Internal Medicine, Department of Medicine, Faculty of Medicine and Dentistry, 2F1 WMC, University of Alberta Hospital, Edmonton, AB, Canada, T6G 2B7
  3. 3College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada, S7N 5C9
  4. 4Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, 2F1 WMC, University of Alberta Hospital, Edmonton, AB, Canada, T6G 2B7
  5. 5Department of Public Health Sciences, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada, T6G 2G3
  1. Correspondence to: J A Johnson jeff.johnson{at}
  • Accepted 13 August 2007


Objective To review the literature on the association between antidiabetic agents and morbidity and mortality in people with heart failure and diabetes.

Design Systematic review and meta-analysis of controlled studies (randomised trials or cohort studies) evaluating antidiabetic agents and outcomes (death and admission to hospital) in patients with heart failure and diabetes.

Data sources Electronic databases, manual reference search, and contact with investigators.

Review methods Two reviewers independently extracted data. Risk estimates for specific treatments were abstracted and pooled estimates derived by meta-analysis where appropriate.

Results Eight studies were included. Three of four studies found that insulin use was associated with increased risk for all cause mortality (odds ratio 1.25, 95% confidence interval 1.03 to 1.51; 3.42, 1.40 to 8.37 in studies that did not adjust for diet and antidiabetic drugs; hazard ratio 1.66, 1.20 to 2.31; 0.96, 0.88 to 1.05 in the studies that did). Metformin was associated with significantly reduced all cause mortality in two studies (hazard ratio 0.86, 0.78 to 0.97) compared with other antidiabetic drugs and insulin; 0.70, 0.54 to 0.91 compared with sulfonylureas); a similar trend was seen in a third. Metformin was not associated with increased hospital admission for any cause or for heart failure specifically. In four studies, use of thiazolidinediones was associated with reduced all cause mortality (pooled odds ratio 0.83, 0.71 to 0.97, I2=52%, P=0.02). Thiazolidinediones were associated with increased risk of hospital admission for heart failure (pooled odds ratio 1.13 (1.04 to 1.22), I2=0%, P=0.004). The two studies of sulfonylureas had conflicting results, probably because of differences in comparator treatments. Important limitations were noted in all studies.

Conclusion Metformin was the only antidiabetic agent not associated with harm in patients with heart failure and diabetes. It was associated with reduced all cause mortality in two of the three studies.


  • Web references w1-w8 are on

  • Contributors: DTE, FAM, DFB, SRM, RTT, and JAJ helped plan and design the study. DTE, DFB, JV, and JAJ collected the data. DTE conducted the statistical analyses. All authors had access to the data and helped interpret the data. DTE wrote the first draft of the paper. All authors reviewed and revised the paper for important intellectual content and approved the version. DTE led the study, is lead author, and is guarantor.

  • Funding: DTE held a doctoral research award with Canadian Institutes for Health Research (CIHR). SRM and FAM are new investigators with CIHR and are population health investigators with the Alberta Heritage Foundation for Medical Research (AHFMR). FAM and RTT hold the Merck Frosst/Aventis chair in patient health management. JAJ holds a Canada Research chair in diabetes health outcomes, is a health scholar supported by AHFMR, and is chair of a new emerging team (NET) grant to the Alliance for Canadian Health Outcomes Research in Diabetes (ACHORD). The ACHORD NET grant is sponsored by the Canadian Diabetes Association, the Heart and Stroke Foundation of Canada, The Kidney Foundation of Canada, the CIHR (Institute of Nutrition, Metabolism and Diabetes) and the CIHR (Institute of Circulatory and Respiratory Health). The study sponsors played no role in study design or conduct; collection, analysis, interpretation of data; writing of the report; or in the decision to submit the paper for publication.

  • Competing interests: None declared.

  • Ethical approval: Not required.

  • Accepted 13 August 2007
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