COMMENTARY

Do Statins Raise the Risk for Diabetes?

Gregory A. Nichols, PhD

Disclosures

May 04, 2010

Statins and Risk of Incident Diabetes: A Collaborative Meta-analysis of Randomised Statin Trials

Sattar N, Preiss D, Murray HM, et al
Lancet. 2010;375:735-742. Epub 2010 Feb 16.

Study Summary

Using data from 13 clinical trials with 91,140 participants, the investigators conducted a meta-analysis to determine whether a relationship exists between statin use and the development of diabetes. Six of the trials had previously published data for incident diabetes. The other 7 studies had not analyzed or published data on incident diabetes.

For each trial in the meta-analysis, odds ratios and 95% confidence intervals were calculated on the basis of the number of patients who did not have diabetes at baseline and the number who developed incident diabetes. An overall odds ratio was then calculated with a random-effects model meta-analysis. Meta-regression analysis was also used to investigate potential differences (heterogeneity) between trials. Specifically, baseline age, body mass index (BMI), and percentage of change in low-density lipoprotein (LDL) cholesterol were tested.

Of the 91,140 participants without diabetes, 4278 developed incident diabetes over a mean study follow-up of about 4 years. The rate of diabetes in individual trials varied substantially. Of the 13 trials, 2 independently showed positive associations between statin therapy and incident diabetes. In the combined data, 174 more cases of incident diabetes occurred in the groups assigned to statin treatment than in the placebo or standard-care groups, representing a 9% increase in the likelihood of development of diabetes during follow-up. The investigators estimated that this amounted to 1 additional case of diabetes per 255 patients treated with statins over 4 years. The results were nearly identical when the analyses were restricted to placebo-controlled trials. Heterogeneity between trials was low. Although the association between statin therapy and risk for incident diabetes was stronger in trials with older participants, baseline BMI and percent change in LDL cholesterol did not seem to be important factors.

Viewpoint

Although most statin trials to date had not found a relationship between statin use and diabetes incidence, the recent JUPITER (Crestor 20mg Versus Placebo in Prevention of Cardiovascular (CV) Events)[1] trial that reported an increased risk for diabetes in patients assigned to the rosuvastatin arm seconded concerns raised several years ago when the PROSPER (PROspective Study of Pravastatin in the Elderly at Risk)[2] trial reported similar findings with pravastatin. However, most trials had not looked at diabetes as a secondary outcome. The investigators of the current study are to be commended for obtaining access to previously unpublished results, thus eliminating a common flaw in meta-analyses.

With these data, they were able to identify a small but significantly increased risk for incident diabetes associated with statin use. Like observational studies, however, a meta-analysis cannot establish causation; therefore, it is possible that unmeasured factors explain the results. For example, the analysis did not account for baseline glycemic level. This is unlikely to be different between groups in randomized trials, but it is possible or even likely that patients who developed diabetes were more dysglycemic, and that a small "nudge" from statins was enough for them to convert to diabetes. If so, these patients were already at increased cardiovascular risk,[3] in which case treatment with statins would be far more important than the few milligrams per deciliter of fasting glucose that took these patients over the diagnostic threshold for diabetes. It is also important to note that these results do not address whether statins raise blood sugar in people already diagnosed with diabetes, most of whom should already be taking statins.[4]

Abstract

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