High-dose atorvastatin (Lipitor, Pfizer) compared with placebo is associated with a slightly increased risk of new-onset type 2 diabetes, based on one of three large randomized trials, which researchers evaluated and published April 5 in the Journal of the American College of Cardiology. However, baseline fasting glucose level and features of the metabolic syndrome are predictive of new-onset type 2 diabetes across the three trials.
David D. Waters, MD, from the division of cardiology at San Francisco General Hospital, and colleagues sought to examine the incidence and clinical predictors of new-onset type 2 diabetes within three large randomized trials with atorvastatin: TNT, IDEAL and SPARCL.
The researchers used a standard definition of diabetes and excluded patients with prevalent diabetes at baseline. They then identified baseline predictors of new-onset type 2 diabetes, and compared the event rates in patients with and without new-onset type 2 diabetes.
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 type 2 diabetes (9.24 vs. 8.11 percent). In the IDEAL (Incremental Decrease in Endpoints 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 type 2 diabetes (6.4 vs. 5.59 percent). In the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial, new-onset type 2 diabetes 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 percent).
In each of the three trials, the authors reported that baseline fasting blood glucose, body mass index, hypertension and fasting triglycerides were independent predictors of new-onset type 2 diabetes.
“Low HDL cholesterol levels were predictive of new-onset type 2 diabetes mellitus by univariate but not multivariate analysis,” Waters and colleagues wrote. “White blood cell count, a rough marker of inflammation, was a univariate predictor in all three trials but a multivariate predictor only in the TNT trial.” Also, age, sex and smoking were not consistently predictive of new-onset type 2 diabetes.
Across the three trials, major cardiovascular events occurred in 11.3 percent of patients with and 10.8 percent of patients without new-onset type 2 diabetes.
“Although these results do not exclude an increased risk of up to 35 percent and an increased risk might become apparent after longer follow-up, our results suggest that the risk accompanying statin-associated diabetes might not be equivalent to the usual risk of diabetes,” the authors wrote. “Patients who developed thiazide-induced new-onset type 2 diabetes mellitus in the ALLHAT (Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial) were also not at increased risk of a cardiovascular event.”
Waters et al concluded, “The benefits of atorvastatin clearly outweigh the risks in patients with coronary or cerebrovascular disease,” although any potential increased risk of new-onset type 2 diabetes with atorvastatin “might warrant careful monitoring.”
The TNT, IDEAL and SPARCL trials were funded by Pfizer.