title: Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials.
abstract: OBJECTIVE
  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.
authors: Division of Cardiology, San Francisco General Hospital, and University of California at San Francisco, San Francisco, California 94114, USA. dwaters@medsfgh.ucsf.edu
authors: David D
authors: DD
authors: Waters
authors: Jennifer E
authors: JE
authors: Ho
authors: David A
authors: DA
authors: DeMicco
authors: Andrei
authors: A
authors: Breazna
authors: Benoit J
authors: BJ
authors: Arsenault
authors: Chuan-Chuan
authors: CC
authors: Wun
authors: John J
authors: JJ
authors: Kastelein
authors: Helen
authors: H
authors: Colhoun
authors: Philip
authors: P
authors: Barter
mesh_terms: D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced* / Q000453:epidemiology*; D005260:Female; D005544:Forecasting; D006538:Heptanoic Acids / Q000009:adverse effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000009:adverse effects*; D012307:Risk Factors
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin