Intensive-Dose Statins Increase Risk of Diabetes but Lower Cardiovascular Risk Compared to Moderate-Dose Statins

DynaMed Weekly Update - Volume 6, Issue 25

Statins are widely used for treating elevated cholesterol for both primary and secondary prevention of coronary artery disease. One concern about their use has been the possibility of increasing the risk of diabetes. Last year, a randomized trial showed that after 2 months of treatment with atorvastatin, patients had increases in fasting plasma insulin, insulin resistance and hemoglobin A1c levels (J Am Coll Cardiol 2010 Mar 23;55(12):1209), and a systematic review found an increase in the risk of new onset of diabetes of 0.4% with statin use (number needed to harm [NNH] 255) (Lancet 2010 Feb 27;375(9716):735). The increased risk of new-onset of diabetes was confirmed in a subgroup analysis of patients from the SPARCL trial (J Am Coll Cardiol 2011 Apr 5;57(14):1535). This study found new-onset of diabetes in 8.71% with atorvastatin 80 mg/day vs. 6.06% with placebo (p < 0.05, NNH 38) (level 2 [mid-level] evidence).

Now, a pooled analysis of 5 lipid-lowering trials using statins (atorvastatin or simvastatin) with 32,752 patients has found an increased risk of diabetes with high-dose therapy compared to moderate-dose therapy. Diabetes was diagnosed if it was listed as an adverse event, there were 2 or more fasting blood glucose levels > 125 mg/dL, or the patient was started on a glucose-lowering medication. The overall rate of new-onset diabetes was 8.4%. Comparing intensive-dose statin vs. moderate-dose statin, the rate of diabetes was 8.8% vs. 8% (odds ratio of 1.12, 95% CI 1.04-1.22) (level 1 [likely reliable] evidence). By way of comparison, cardiovascular events occurred in 19.1% of patients taking intensive doses and in 21.7% taking moderate doses (odds ratio 0.84, 95% CI 0.75-0.94). Overall, intensive-dose statin use had a number needed to harm (NNH) of 498 per year for the risk of new-onset diabetes and a number needed to treat (NNT) of 155 per year for the benefit of decreased cardiovascular events (JAMA 2011 Jun 22;305(24):2556).

For more information, see the Risk factors for diabetes mellitus type 2 topic in DynaMed.