Lower Intensified Target LDL-c Level of Statin Therapy Results in a Higher Risk of Incident Diabetes: A Meta-Analysis

Background: 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 determine whether statin therapy with lower intensive-target LDL-c level contributes to higher risk of new-onset diabetes. Methods: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled endpoint trials of statins conducted from 1966 to 2012. We included trials with more than 1000 participants who were followed up for at least 2 years. The included trials were stratified by the target LDL-c level. I2 statistic was used to measure heterogeneity between trials. We further calculated risk estimates with random-effect meta-analysis. Meta-regression was used to identify the potential risk factors of statin-induced diabetes. Results: Fourteen trials with a total of 95 102 non-diabetic participants were included. The risks elevated by 33% [odds ratio (OR) = 1.33; 95% confidence interval (CI) 1.14–1.56; I2 = 7.7%] and 16% (OR = 1.16; 95% CI 1.06–1.28; I2 = 0.0%) when the intensified target LDL-c levels were ≤1.8 mmol/L and 1.8–2.59 mmol/L, respectively. The risk of incident diabetes did not increase when the target LDL-c level was ≥2.59 mmol/L. 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. Conclusion: A lower intensified target LDL-c level of statin therapy resulted in a higher risk of incident diabetes.