Cholesterol Drug Atorvastatin Raises Chance of Diabetes

Summary
This review was done to determine the clinical predictors of new-onset type 2 diabetes mellitus by analyzing three large randomized previous studies involving the use of the cholesterol-reducing drug atorvastatin. It was found that increasing doses of atorvastatin led to higher incidence of the new-onset type 2 diabetes mellitus. In one of the studies, atorvastatin was compared with placebo, revealing that high doses of this medication could lead to increase in the incidence of type 2 diabetes mellitus. It was also clear that initial blood glucose levels and a few clinical symptoms were the predictors of the new-onset type 2 diabetes mellitus.

Introduction
Increase in the incidence of type 2 diabetes has been attributed to various medications taken for associated diseases like kidney, heart and hormonal disorders. Around 13 previous studies involving statins or cholesterol-reducing drugs have stated that statin therapy has increased the incidence of new-onset type 2 diabetes. These trials showed that statins caused a high incidence of new-onset type 2 diabetes in the older participants. Body mass indices and cholesterol levels, which were thought to be predictors for the diabetic onset, were not proven to be good predictors for the disease. No other predictors were considered in these studies and only one of them included atorvastatin, a common drug of this class. Thus, this study was performed by incorporating a review of three larger studies that compared the incidence of new-onset type 2 diabetes on treatment only with atorvastatin. The baseline investigations used to classify patients, as those with new-onset type 2 diabetes were well defined and the predictors of the diabetic onset were ascertained.

Methodology
Three large randomized studies on the drug atorvastatin were compared in this review. The first study was Treating to New Targets (TNT) trial, where the incidence of diabetes was compared between patients taking atorvastatin 80 mg/day with those patients taking atorvastatin 10 mg/day. In the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) trial, incidence of diabetes was compared between  patients being treated with atorvastatin and those being treated with another drug called simvastatin. The final and the only study with a placebo group was the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPRACL) trial. The parameters varied among these three randomized studies. Thus, statistical methods were used to analyze the data and an incidence of new-onset type 2 diabetes was related to the use of atorvastatin.

Results
* A total of 8.6 percent, 5.9 percent and 7.3 percent patients were diagnosed with new-onset type 2 diabetes in the TNT trial, the IDEAL trial and the SPARCL trial, respectively.
* Those patients with higher blood pressure, blood glucose, body mass index, white blood cell count and cholesterol levels were more likely to develop the new-onset type 2 diabetes.
* The rates of the new-onset type 2 diabetes were 9.24 percent with those taking 80 mg atorvastatin, but 8.11 percent with those on 10 mg atorvastatin in the TNT trial. Similarly, in the SPARCL trial, it was 8.71 percent with those taking atorvastatin compared to 6.06 percent in the placebo group.
* Blood glucose levels constituted the strongest predictor of the new-onset type 2 diabetes in all the three trials.

Shortcomings/Next steps
Most of the patients were Caucasians; thus, there was an inability to generalize the results in these three trials. A few studies showed high incidence of new-onset type 2 diabetes in Japanese patients, which was not accounted for in this study. Only one trial considered in this study had a placebo group. There was no significant association between statins and the onset of diabetes in two of the studies, which considered the use of 80 mg/day of atorvastatin.

Conclusion
The comparison of data from three large randomized studies highlights the influence of high-dose atorvastatin on the incidence of new-onset type 2 diabetes. However, blood glucose levels, blood pressure, cholesterol levels and body mass indices of patients could predict the onset of diabetes. Blood glucose level was found to be the strongest predictor amongst the others. The cause of the new-onset type 2 diabetes could be attributed to lowered insulin sensitivity in the liver due to atorvastatin. However, no experimental data exists to support this hypothesis. The influence and benefits of atorvastatin on the patients with new-onset type 2 diabetes in reducing the incidence of stroke and heart attack far outweigh the risk of inducing diabetes in them. Thus, atorvastatin must be made mandatory for patients with heart diseases or those having previous history of stroke.

For More Information:
Predictors of New-onset Diabetes in Patients Treated with Atorvastatin
Publication Journal: Journal of the American College of Cardiology, 2011
By David Waters, MD; Jennifer Ho, MD; University of California, San Francisco

*FYI Living Lab Reports Are Summaries of the Original Research.

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