Abstract

BackgroundA 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.MethodsMedline, 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. I 2 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.ResultsFourteen 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; I 2 = 7.7%] and 16% (OR = 1.16; 95% CI 1.06–1.28; I 2 = 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.ConclusionA lower intensified target LDL-c level of statin therapy resulted in a higher risk of incident diabetes.

Highlights

  • Statin drugs are widely used in the evidence-based lowering of cardiovascular disease (CVD) risk

  • The results showed that intensive low-density lipoprotein cholesterol (LDL-c) lowering with statin use lead to a 19% increased risk of incident diabetes

  • This study aims to investigate the relationship between target LDL-c level of statin use and new-onset type 2 diabetes mellitus (T2DM) and identify the potential predictors of statin-induced diabetes

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Summary

Introduction

Statin drugs are widely used in the evidence-based lowering of cardiovascular disease (CVD) risk. A recent meta-analysis of 13 trials showed that statin therapy is associated with an increased risk of developing type 2 diabetes mellitus (T2DM) [4]. Another meta-analysis combined five trials reported that an excess incidence of new-onset T2DM occurred in patients treated with intensive-dose statin [5]. A recent meta-analysis has reported that intensive-dose statin drug increases the risk of incident diabetes. This study aimed to determine whether statin therapy with lower intensive-target LDL-c level contributes to higher risk of new-onset diabetes

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