Author + information
- Received July 28, 2010
- Revision received October 4, 2010
- Accepted October 11, 2010
- Published online April 5, 2011.
- David D. Waters, MD⁎,⁎ (, )
- Jennifer E. Ho, MD⁎,
- David A. DeMicco, DPharm†,
- Andrei Breazna, PhD†,
- Benoit J. Arsenault, PhD‡,
- Chuan-Chuan Wun, PhD†,
- John J. Kastelein, MD, PhD‡,
- Helen Colhoun, MD, PhD§ and
- Philip Barter, MD, PhD∥
- ↵⁎Reprint requests and correspondence:
Dr. David D. Waters, Division of Cardiology, San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, California 94114
Objectives We sought to examine the incidence and clinical predictors of new-onset type 2 diabetes mellitus (T2DM) within 3 large randomized trials with atorvastatin.
Background Statin therapy might modestly increase the risk of new-onset T2DM.
Methods We used a standard definition of diabetes and excluded patients with prevalent diabetes at baseline. We identified baseline predictors of new-onset T2DM and compared the event rates in patients with and without new-onset T2DM.
Results In the TNT (Treating to New Targets) trial, 351 of 3,798 patients randomized to 80 mg of atorvastatin and 308 of 3,797 randomized to 10 mg developed new-onset T2DM (9.24% vs. 8.11%, adjusted hazard ratio [HR]: 1.10, 95% confidence interval [CI]: 0.94 to 1.29, p = 0.226). In the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) trial, 239 of 3,737 patients randomized to atorvastatin 80 mg/day and 208 of 3,724 patients randomized to simvastatin 20 mg/day developed new-onset T2DM (6.40% vs. 5.59%, adjusted HR: 1.19, 95% CI: 0.98 to 1.43, p = 0.072). In the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial, new-onset T2DM developed in 166 of 1,905 patients randomized to atorvastatin 80 mg/day and in 115 of 1,898 patients in the placebo group (8.71% vs. 6.06%, adjusted HR: 1.37, 95% CI: 1.08 to 1.75, p = 0.011). In each of the 3 trials, baseline fasting blood glucose, body mass index, hypertension, and fasting triglycerides were independent predictors of new-onset T2DM. Across the 3 trials, major cardiovascular events occurred in 11.3% of patients with and 10.8% of patients without new-onset T2DM (adjusted HR: 1.02, 95% CI: 0.77 to 1.35, p = 0.69).
Conclusions High-dose atorvastatin treatment compared with placebo in the SPARCL trial is associated with a slightly increased risk of new-onset T2DM. Baseline fasting glucose level and features of the metabolic syndrome are predictive of new-onset T2DM across the 3 trials.
The TNT, IDEAL, and SPARCL trials were funded by Pfizer, Inc. The SPARCL Steering Committee approved the use of SPARCL trial data for this analysis, but interpretation and conclusions contained herein do not necessarily represent the position of the committee. Dr. Waters has consulted for Anthera, Aegerion, Cortria, CSL, Genentech, Pfizer, and Roche; received honoraria from Bristol-Myers Squibb and Pfizer; participated in clinical trials sponsored by Biosante, Merck Schering-Plough, Pfizer, and Roche; and owns stock options in Anthera. Dr. Kastelein receives lecture fees from Pfizer and sits on the IDEAL Steering Committee. Dr. Colhoun receives research funding from and is on the Speakers' Bureau for Pfizer. Dr. Barter has consulted for AstraZeneca, CSL, Merck, Pfizer, Roche, and Sanofi-Aventis; received honoraria from Abbott, AstraZeneca, Merck, Pfizer, and Roche; and participated in clinical trials sponsored by AstraZeneca, Merck, Pfizer, and Roche. Drs. DeMicco, Breazna, and Wun are Pfizer employees. All other authors have reported that they have no relationships to disclose.
- Received July 28, 2010.
- Revision received October 4, 2010.
- Accepted October 11, 2010.
- American College of Cardiology Foundation