ArticlesStatins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials
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To resolve this uncertainty, we investigated this effect by undertaking a meta-analysis of all available published and unpublished data from large placebo-controlled and standard-care-controlled statin trials.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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