Letters Section Editor: Jody W. Zylke, MD, Senior Editor.
Author Affiliations: BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (Dr Preiss) (firstname.lastname@example.org); Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (Dr Seshasai); and Division of Cardiac and Vascular Sciences, St George's University of London, London, United Kingdom (Dr Ray).
In Reply: We agree with Dr McEvoy that meta-analysis, by design, cannot establish causation, although the fact that our 2 meta-analyses have included data from 18 randomized trials for more than 120 000 patients1 suggests that the link between statin therapy and new-onset diabetes may be causal. Other proposed explanations for our observations have included survival bias, differential ascertainment of diabetes between trial groups (patients experiencing more adverse effects in 1 group leading them to interact with clinicians more often), and the possibility that patients in some trials were aware of allocated treatment (leading those who receive intensive therapy to adopt poorer lifestyles with resultant weight gain). However, we demonstrated that hazard ratios and odds ratios for new-onset diabetes were identical and that the 25% and 44% increases in new-onset diabetes noted in JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; rosuvastatin, 20 mg, vs placebo) and SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels; atorvastatin, 80 mg, vs placebo),2,3 respectively, occurred despite almost identical numbers of adverse events between treatment groups. Data from JUPITER show that those individuals receiving the statin were only marginally (0.3-kg) heavier than those receiving placebo at the end of the trial (an unlikely explanation for the observed 25% increase in diabetes). The biological plausibility of statins affecting glucose homeostasis is supported by studies from an animal model that suggest a possible effect on insulin signaling.4
Preiss D, Seshasai SRK, Ray KK. Statin Therapy Dose and Risk of New-Onset Diabetes—Reply. JAMA. 2011;306(12):1325-1326. doi:10.1001/jama.2011.1355