Risk of Incident Diabetes With Intensive-Dose Compared With Moderate-Dose Statin Therapy

Clinical Review
JAMA. 2011;305(24):            2556-2564      doi: 10.1001/jama.2011.860

Risk of Incident Diabetes With Intensive-Dose Compared With Moderate-Dose Statin Therapy

A Meta-analysis

  1. David Preiss, MRCP
  2. Sreenivasa Rao Kondapally Seshasai, MD
  3. Paul Welsh, PhD
  4. Sabina A. Murphy, MPH
  5. Jennifer E. Ho, MD
  6. David D. Waters, MD;
  7. David A. DeMicco, DPharm
  8. Philip Barter, MD, PhD
  9. Christopher P. Cannon, MD
  10. Marc S. Sabatine, MD, MPH
  11. Eugene Braunwald, MD
  12. John J. P. Kastelein, MD, PhD
  13. James A. de Lemos, MD
  14. Michael A. Blazing, MD
  15. Terje R. Pedersen, MD, PhD
  16. Matti J. Tikkanen, MD, PhD
  17. Naveed Sattar, MD, PhD
  18. Kausik K. Ray, MD
[+] Author Affiliations

  1. Author Affiliations: BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (Drs Preiss, Welsh, and Sattar); Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (Dr Seshasai); TIMI Study Group, Cardiovascular Division, Harvard Medical School, Boston, Massachusetts (Ms Murphy and Drs Cannon, Sabatine, and Braunwald); Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Boston (Dr Ho); Department of Medicine, University of California, San Francisco (Dr Waters); Global Pharmaceuticals, Pfizer, New York, New York (Dr DeMicco); Heart Research Institute, Sydney, Australia (Dr Barter); Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands (Dr Kastelein); Division of Cardiology, University of Texas Southwestern Medical Center, Dallas (Dr de Lemos); Duke Clinical Research Institute, Durham, North Carolina (Dr Blazing); University of Oslo and Centre for Preventative Medicine, Oslo University Hospital, Ullevål, Oslo, Norway (Dr Pedersen); University of Helsinki and Division of Cardiology, Helsinki University Hospital, and Folkhälsan Research Center, Helsinki, Finland (Dr Tikkanen); and Division of Cardiac and Vascular Sciences, St George’s University of London, London, United Kingdom (Dr Ray).


Context A recent meta-analysis demonstrated that statin therapy is associated with excess risk of developing diabetes mellitus.
Objective To investigate whether intensive-dose statin therapy is associated with increased risk of new-onset diabetes compared with moderate-dose statin therapy.
Data Sources We identified relevant trials in a literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (January 1, 1996, through March 31, 2011). Unpublished data were obtained from investigators.
Study Selection We included randomized controlled end-point trials that compared intensive-dose statin therapy with moderate-dose statin therapy and included more than 1000 participants who were followed up for more than 1 year.
Data Extraction Tabular data provided for each trial described baseline characteristics and numbers of participants developing diabetes and experiencing major cardiovascular events (cardiovascular death, nonfatal myocardial infarction or stroke, coronary revascularization). We calculated trial-specific odds ratios (ORs) for new-onset diabetes and major cardiovascular events and combined these using random-effects model meta-analysis. Between-study heterogeneity was assessed using the I2 statistic.
Results In 5 statin trials with 32 752 participants without diabetes at baseline, 2749 developed diabetes (1449 assigned intensive-dose therapy, 1300 assigned moderate-dose therapy, representing 2.0 additional cases in the intensive-dose group per 1000 patient-years) and 6684 experienced cardiovascular events (3134 and 3550, respectively, representing 6.5 fewer cases in the intensive-dose group per 1000 patient-years) over a weighted mean (SD) follow-up of 4.9 (1.9) years. Odds ratios were 1.12 (95% confidence interval [CI], 1.04-1.22; I2 = 0%) for new-onset diabetes and 0.84 (95% CI, 0.75-0.94; I2 = 74%) for cardiovascular events for participants receiving intensive therapy compared with moderate-dose therapy. As compared with moderate-dose statin therapy, the number needed to harm per year for intensive-dose statin therapy was 498 for new-onset diabetes while the number needed to treat per year for intensive-dose statin therapy was 155 for cardiovascular events.
Conclusion In a pooled analysis of data from 5 statin trials, intensive-dose statin therapy was associated with an increased risk of new-onset diabetes compared with moderate-dose statin therapy.

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