Key result
High-dose atorvastatin increases new-onset type 2 diabetes risk by ~37% vs placebo in SPARCL.
Why the study?
Does high-dose atorvastatin increase the risk of new-onset type 2 diabetes compared to lower-dose statins or placebo in patients without baseline diabetes?
RCT (n=18,859)
randomized
Yes
Does high-dose atorvastatin increase the risk of new-onset type 2 diabetes compared to lower-dose statins or placebo in patients without baseline diabetes?
Hazard Ratio: 1.37 (95% CI 1.08–1.75)
Absolute Event Rate: 8.71% vs 6.06%
p-value: p=0.011
High-dose atorvastatin is associated with a slightly increased risk of new-onset type 2 diabetes compared to placebo, with baseline metabolic features strongly predicting this risk.
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.
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Waters et al. (2011) conducted an RCT in Patients at risk for cardiovascular events without prevalent diabetes (n=18,859). Atorvastatin vs. Placebo (SPARCL), atorvastatin 10 mg (TNT), or simvastatin 20 mg (IDEAL) was evaluated on New-onset type 2 diabetes mellitus (SPARCL trial comparison vs placebo) (HR 1.37, 95% CI 1.08-1.75, p=0.011). High-dose atorvastatin (80 mg/day) compared with placebo was associated with an increased risk of new-onset type 2 diabetes (8.71% vs 6.06%; HR 1.37, 95% CI 1.08-1.75, p=0.011) in the SPARCL trial.
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