Preventive cardiology
Meta-Analysis of Impact of Different Types and Doses of Statins on New-Onset Diabetes Mellitus

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Recent reports indicate that statins are associated with an increased risk for new-onset diabetes mellitus (DM) compared with placebo and that this relation is dose dependent. The aim of this study was to perform a comprehensive network meta-analysis of randomized controlled trials (RCTs) investigating the impact of different types and doses of statins on new-onset DM. RCTs comparing different types and doses of statins with placebo were searched for using the MEDLINE, Embase, and Cochrane databases. A search of RCTs pertinent to this meta-analysis covering the period from November 1994 to October 2012 was conducted by 2 independent investigators using the MEDLINE, Cochrane, Google Scholar, and Embase databases as well as abstracts and presentations from major cardiovascular meetings. Seventeen RCTs reporting the incidence of new-onset DM during statin treatment and including a total of 113,394 patients were identified. The RCTs compared either a statin versus placebo or high-dose versus moderate-dose statin therapy. Among different statins, pravastatin 40 mg/day was associated with the lowest risk for new-onset DM compared with placebo (odds ratio 1.07, 95% credible interval 0.86 to 1.30). Conversely, rosuvastatin 20 mg/day was numerically associated with 25% increased risk for DM compared with placebo (odds ratio 1.25, 95% credible interval 0.82 to 1.90). The impact on DM appeared to be intermediate with atorvastatin 80 mg/day compared with placebo (odds ratio 1.15, 95% credible interval 0.90 to 1.50). These findings were replicated at moderate doses. In conclusion, different types and doses of statins show different potential to increase the incidence of DM.

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Methods

Established methods were used in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement for reporting systematic reviews and meta-analyses in health care interventions.5 A search of pertinent RCTs conducted from November 1994 to October 2012 was performed by 2 independent investigators covering the MEDLINE, Cochrane, Google Scholar, and Embase databases as well as abstracts and presentations from major cardiovascular meetings, using the search string

Results

The flow diagram of the study is shown in Figure 1. Seventeen RCTs8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 fulfilling the eligibility criteria and comprising a total of 113,394 patients were eventually included for data abstraction. Table 1 lists the main characteristics of the included studies. Fourteen RCTs compared a statin with placebo, and 3 studies compared high- with moderate-dose statin therapy. The high daily doses of statins used in the RCTs were atorvastatin

Discussion

The present study is the largest and most comprehensive study thus far comparing rates of new-onset DM among different types and doses of statins. The main findings derived from a population of 113,394 patients were as follows: (1) there was a gradient for the risk for new-onset DM across different types and doses of statins, (2) pravastatin therapy was numerically associated with the lowest rate of new-onset DM compared with other statins, whereas treatment with rosuvastatin was associated

Acknowledgment

The present study is a project of Systematic Investigation and Research on Interventions and Outcomes (SIRIO)–MEDICINE, an international scientific group committed to research and innovation in medicine.

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