17 February 2010 

Statin therapy increases the risk of diabetes and patients taking the drugs should have their blood glucose monitored on a regular basis, according to articles published in the Lancet today.

A meta-analysis of 13 statin trials with more than 90,000 patients found that use of the drugs was associated with a 9% increased risk of diabetes over four years. The risk seemed higher in trials with older participants.

In absolute terms this represents one extra case of diabetes per thousand treatment years, which means that “if you treat 255 patients for four years with a statin, one additional patient would develop diabetes than if they had not been treated with a statin,” an accompanying editorial notes.

It says the diabetes risk is low in absolute terms and when compared with the reduction in coronary events seen with statins. “Therefore the benefit in preventing total vascular events
to the risk of diabetes is a ratio of about 9:1 in favour of the cardiovascular benefit—the benefit seems to greatly outweigh the risk,”

However, the commentary says this newly identified risk of diabetes does warrant monitoring, “and, as such, in addition to periodic monitoring of liver-function tests and creatine kinase, it seems reasonable to add glucose to the list of tests to monitor in older patients who are on statins.”

The researchers say the metaanalysis was done to clarify conflicting results from other trials about the development of diabetes with statin therapy. They say some statins may have a detrimental effect on glucose metabolism via the glucosetransporter-4 mechanism, but the meta-analysis findings do not show conclusively that there is a causal link between statin use and the development of diabetes.

The Lancet, Early Online Publication, 17 February 2010

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

Author: Prof Naveed Sattar PhD et al.

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 We aimed to establish by a meta-analysis of published and unpublished data whether any relation exists between statin use and development of diabetes.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.