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  3. Higher potency statins and the risk of new diabetes: multicentre, observational study of administrative databases
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Research

Higher potency statins and the risk of new diabetes: multicentre, observational study of administrative databases

BMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g3244 (Published 29 May 2014) Cite this as: BMJ 2014;348:g3244
  1. Colin R Dormuth, assistant professor1,
  2. Kristian B Filion, assistant professor2,
  3. J Michael Paterson, scientist3,
  4. Matthew T James, assistant professor4,
  5. Gary F Teare, director of measurement and analysis5,
  6. Colette B Raymond, research scientist6,
  7. Elham Rahme, associate professor7,
  8. Hala Tamim, associate professor8,
  9. Lorraine Lipscombe, adjunct scientist3
  10. for the Canadian Network for Observational Drug Effect Studies (CNODES) Investigators
  1. 1Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Victoria, BC V8W 1Y2, Canada
  2. 2Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Canada
  3. 3Institute for Clinical Evaluative Sciences, Toronto, Canada
  4. 4Department of Medicine, University of Calgary, Calgary, Canada
  5. 5Health Quality Council, Saskatoon, Canada
  6. 6Manitoba Centre for Health Policy, University of Manitoba, Winnipeg, Canada
  7. 7Department of Medicine, McGill University, Montreal, Canada
  8. 8School of Kinesiology and Health Science, York University, Toronto, Canada
  1. Correspondence to: C R Dormuth colin.dormuth{at}ti.ubc.ca
  • Accepted 25 April 2014

Abstract

Objective To evaluate the incremental increase in new onset diabetes from higher potency statins compared with lower potency statins when used for secondary prevention.

Design Eight population based cohort studies and a meta-analysis.

Setting Six Canadian provinces and two international databases from the UK and US.

Participants 136 966 patients aged ≥40 years newly treated with statins between 1 January 1997 and 31 March 2011.

Methods Within each cohort of patients newly prescribed a statin after hospitalisation for a major cardiovascular event or procedure, we performed as-treated, nested case-control analyses to compare diabetes incidence in users of higher potency statins with incidence in users of lower potency statins. Rate ratios of new diabetes events were estimated using conditional logistic regression on different lengths of exposure to higher potency versus lower potency statins; adjustment for confounding was achieved using high dimensional propensity scores. Meta-analytic methods were used to estimate overall effects across sites.

Main outcome measures Hospitalisation for new onset diabetes, or a prescription for insulin or an oral antidiabetic drug.

Results In the first two years of regular statin use, we observed a significant increase in the risk of new onset diabetes with higher potency statins compared with lower potency agents (rate ratio 1.15, 95% confidence interval 1.05 to 1.26). The risk increase seemed to be highest in the first four months of use (rate ratio 1.26, 1.07 to 1.47).

Conclusions Higher potency statin use is associated with a moderate increase in the risk of new onset diabetes compared with lower potency statins in patients treated for secondary prevention of cardiovascular disease. Clinicians should consider this risk when prescribing higher potency statins in secondary prevention patients.

Footnotes

  • This study was made possible through data sharing agreements between CNODES member research centres and the respective provincial governments of Alberta, Manitoba, Nova Scotia, Ontario, Quebec, and Saskatchewan. The opinions, results, and conclusions reported in this paper are those of the authors. No endorsement by the provincial governments is intended or should be inferred. We acknowledge the important contributions of the CNODES collaborators and assistants at each site: Richard Morrow (BC, MarketScan), James Zhang (Alberta), Alomgir Hossain (Saskatchewan), Matthew Dahl (Manitoba), Fangyun Wu (Ontario), Hacene Nedjar (Quebec), Steve Doucette and Yan Wang (Nova Scotia), and Sophie Dell’Aniello (CPRD). We also acknowledge the assistance of Dr James Wright, who provided his expert understanding of randomised trials of statins.

  • The Canadian Network for Observational Drug Effect Studies (CNODES) Investigators are: Samy Suissa (principal investigator); Colin Dormuth (British Columbia); Brenda Hemmelgarn (Alberta); Gary Teare (Saskatchewan); Patricia Martens and Patricia Caetano (Manitoba); David Henry and Michael Paterson (Ontario); Jacques LeLorier (Québec); Adrian Levy (Nova Scotia); Pierre Ernst (UK General Practice Research Database (CPRD)); Robert Platt (Methods); and Ingrid Sketris (Knowledge Translation).

  • Contributors: CRD oversaw the development of the study protocol and the creation of a data analysis plan that was adapted for use in each jurisdiction and each dataset. All authors contributed to discussions on protocol development and provided critical revisions to the manuscript. LL defined the diabetes outcome. KBF, JMP, GFT, and HT contributed to study design issues. CRD drafted the manuscript and incorporated co-authors’ suggestions, and is the guarantor of the manuscript. The final manuscript was approved by the publications subcommittee of CNODES.

  • Funding: CNODES is a collaborating centre of the Drug Safety and Effectiveness Network (DSEN), funded by the Canadian Institutes of Health Research (Grant No DSE-111845). The funding source was not involved in the writing of the manuscript or the decision to submit it for publication.

  • Ethical approval: Approval for each study was obtained from the respective academic institutions at each site.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; ER has received grants and consultant fees from Pfizer Canada that were unrelated to this study, and MTJ received an honorarium for a presentation at an industry sponsored conference by Amgen unrelated to this study; no other relationships or activities that could appear to have influenced the submitted work.

  • Data sharing: CNODES is not permitted to release individual level data or aggregated data with small cell sizes. The scientific protocol for this analysis is available on request.

  • Transparency: The lead author (the manuscript’s guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

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