Elsevier

The Lancet

Volume 375, Issue 9716, 27 February–5 March 2010, Pages 735-742
The Lancet

Articles
Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials

https://doi.org/10.1016/S0140-6736(09)61965-6Get rights and content

Summary

Background

Trials of statin therapy have had conflicting findings on the risk of development of diabetes mellitus in patients given statins. We aimed to establish by a meta-analysis of published and unpublished data whether any relation exists between statin use and development of diabetes.

Methods

We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1994 to 2009, for randomised controlled endpoint trials of statins. We included only trials with more than 1000 patients, with identical follow-up in both groups and duration of more than 1 year. We excluded trials of patients with organ transplants or who needed haemodialysis. We used the I2 statistic to measure heterogeneity between trials and calculated risk estimates for incident diabetes with random-effect meta-analysis.

Findings

We identified 13 statin trials with 91 140 participants, of whom 4278 (2226 assigned statins and 2052 assigned control treatment) developed diabetes during a mean of 4 years. Statin therapy was associated with a 9% increased risk for incident diabetes (odds ratio [OR] 1·09; 95% CI 1·02–1·17), with little heterogeneity (I2=11%) between trials. Meta-regression showed that risk of development of diabetes with statins was highest in trials with older participants, but neither baseline body-mass index nor change in LDL-cholesterol concentrations accounted for residual variation in risk. Treatment of 255 (95% CI 150–852) patients with statins for 4 years resulted in one extra case of diabetes.

Interpretation

Statin therapy is associated with a slightly increased risk of development of diabetes, but the risk is low both in absolute terms and when compared with the reduction in coronary events. Clinical practice in patients with moderate or high cardiovascular risk or existing cardiovascular disease should not change.

Funding

None.

Introduction

Statin therapy is effective for reduction of cardiovascular events1, 2 and is generally recognised as being safe and well tolerated.3 However, researchers of six large randomised placebo-control trials4, 5, 6, 7, 8, 9 have reported conflicting results about the development of diabetes in patients taking such drugs. In the JUPITER 4 trial, 17 802 adults with no clinical or biochemical diagnosis of diabetes based on fasting glucose concentrations were assigned rosuvastatin or placebo for a median of 1·9 years. Significantly more individuals in the statin group than in the placebo group developed diabetes.

By contrast, results from the WOSCOPS5 study suggested that pravastatin therapy might reduce the frequency of diabetes. These findings have raised questions about the safety of long-term use of statins,10 and led to calls for a systematic exploration of the possible effect of statin therapy on incident diabetes.11 Overestimation of clinical benefit or underestimation of risk is potentially of major public health importance. To resolve this uncertainty, we investigated this effect by undertaking a meta-analysis of all available published and unpublished data from large placebo-controlled and standard-care-controlled statin trials.

Section snippets

Search strategy and selection criteria

We gathered data from large placebo and standard-care-controlled endpoint trials of statins that were designed to assess the effect of statin treatment on cardiovascular endpoints in stable individuals—ie, no patients with organ transplants or receiving haemodialysis. We excluded trials comparing statins (either different statins or doses of the same statin), those in patients with diabetes, trials assessing change in surrogate markers of cardiovascular disease, and those that had recruited

Results

We identified 13 clinical trials providing data for 91 140 non-diabetic participants of whom 4278 developed incident diabetes (figure 1). The mean study follow-up was about 4 years (weighted average; table). Rate of diabetes in individual trials varied substantially (figure 2). Of the 13 trials, two (JUPITER and PROSPER) individually showed positive associations between statin therapy and incident diabetes (figure 2). For combined data (table), we identified 174 more cases of incident diabetes

Discussion

The results of this meta-analysis show that individuals assigned statins were at slightly increased risk of diabetes compared with those assigned placebo or standard care. This risk seemed higher in trials with older participants. Results from only those trials that used fasting glucose measurements and were placebo-controlled were consistent with this finding. We identified no apparent difference between hydrophilic and lipophilic statins in the association with diabetes risk. These results do

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