| Objectives:A recent meta-analysis has reported that intensive-dose statin drug increases the risk of incident diabetes. However, doubling of the statin dose generates only a further 6% decrease in low-density lipoprotein cholesterol (LDL-c) on average. This study aimed to identify whether a relationship exists between intensive LDL-c lowering of statin use and incident diabetes and determine the risk factors of statin-induced diabetes.Methods:Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled endpoint trials (RCTs) of statins conducted from 1966 to October 2012. Trials which compared statin with placebo or standard-care on the effect cardiovascular disease were included. And trials either comparing different statins or different doses of the same statin, trials in patients with diabetes, trials which had recruited 1000 or fewer patients and trials with less than 2 years’ follow up were excluded. Two independent reviewers performed the search and the the two reviewers consulted a third reviewer to settle any discrepancies. Improved Jadad score was used to evaluate the quality of the included studies. The I2 statistic (with 95% CIs), which is derived from Cochran’s Q[100×(Q-df+Q)] is used to measure heterogeneity between trials by statal 1.0, and calculated a relative risk (RR) with a random-effect model for meta-analysis. Then the included trials were stratified by the target LDL-c level and relative LDL-c reduction. Meta-regression was used to identify the potential risk factors of statin-induced diabetes.Results:Totally, fourteen trials with a total of 95,102 non-diabetic participants were included. Among 95,102 participants,4,559 patients (2,393 assigned to statins and 2,167 to placebo) developed diabetes during a mean of four years. Intensive LDL-c lowering with statin therapy was associated with a 17% increase in risk for diabetes (RR=1.17; 95% confidence interval (CI)=1.09 to 1.26), with little heterogeneity between trials. In absolute terms, one additional case of diabetes per 130 patients was treated with statin for four years. The risks elevated by 32%(RR=1.32; 95% CI=1.15-1.51) and 15%(RR=1.15; 95% CI=1.05-1.25) when the intensified target LDL-c levels were <1.8 mmol/L and 1.8-2.6 mmol/L, respectively. The risk of incident diabetes did not increase when the target LDL-c level more than 2.6 mmol/L. As to LDL-c reduction, the risks of incident diabetes elevate by 12%(RR=1.12; 95% CI 1.01-1.24) and 28% (RR=1.28; 95% CI 1.13-1.45) when relative LDL-c reduction were 30-40% and 40-50%, respectively. Compare to placebo group, the risk of incident diabetes in statin group did not increase when LDL-c reduction less than 30%. Apart from age, female, and baseline level of total cholesterol, meta-regression analysis showed that the target and baseline levels of LDL-c and relative LDL-c reduction were predictors of statin-induced diabetes.Conclusions:Intensive LDL-c lowering with statin therapy led to an excess risk of incident diabetes. Although the risk of new-onset diabetes in patients is much lower than the benefit from intensive LDL-c lowering with statin therapy, incident diabetes should be considered to weigh the pros and cons when LDL-c reaches a lower level, e.g., less than 1.8 mmol/L or relative LDL-c reduction more than 30%, especially in primary prevention low-risk patients. |
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