Intensive-dose statin therapy may increase diabetes risk

Intensive-dose statin therapy appears to be associated with an increased risk of new-onset diabetes compared with moderate-dose therapy, according to a meta-analysis of data from 5 statin trials published in the June 22/29 issue of JAMA.

David Preiss, MRCP, of the University of Glasgow, United Kingdom, and colleagues examined the associations of intensive-dose statin therapy versus moderate-dose therapy with the development of diabetes and the occurrence of major cardiovascular events.

Though statin therapy has been shown to significantly reduce cardiovascular events, the researchers note that findings from several trials suggest there may be a dose-dependant effect and that patients treated with intensive-dose statin regimens are at a higher risk for developing diabetes.

To evaluate this association, the researchers searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for studies that included 1,000 or more participants exposed to statin therapy who were followed up for at least 1 year. Five trials were included in their final analysis. The researchers were provided the data for incident diabetes and major cardiovascular events from the investigators on each of the 5 trials, as well as key end points on factors associated with diabetes risk, such as body mass index (BMI), high-density lipoprotein (HDL) cholesterol, triglycerides, age, and fasting plasma glucose (FPG, where available) above and below the trial medians to further ascertain whether any specific subgroups of patients were at greater risk of developing the disease.

Data was collected on 32,752 nondiabetic participants who were followed for an average of 4.9 years, during which 2,749 participants developed diabetes (1,449 of whom were assigned to intensive-dose therapy and 1,300 to moderate-dose therapy) and 6,684 experienced a major cardiovascular event (3,134 of whom were assigned to intensive-dose therapy and 3,550 to moderate-dose therapy). There were 149 more cases of incident diabetes in participants receiving intensive statin treatment than in those receiving moderate-dose therapy (OR=1.12; 95% CI, 1.04–1.22). Among the patients receiving intensive-dose therapy, researchers found 416 fewer patients with cardiovascular events (OR=0.84; 95% CI, 0.75–0.94).

Though intensive-dose statin therapy was associated with fewer major cardiovascular events, it was also associated with a higher incidence of new-onset diabetes when compared with moderate-dose therapy upon analysis. However, researchers did not establish a potential mechanism to explain the findings of a higher incidence of diabetes with intensive-dose therapy. They suggested that it is possible that statins may influence muscle or liver insulin action directly, which would result in a higher risk for developing diabetes. In addition, an analysis of subgroups did not establish whether a specific group of individuals is more at risk or whether statin therapy is associated with a generalized tendency for an increase in diabetes risk.

"Our findings suggest that clinicians should be vigilant for the development of diabetes in patients receiving intensive statin therapy," the authors wrote. "In conclusion, this meta-analysis extends earlier findings of an increased incidence of diabetes with statin therapy by providing evidence of a dose-dependent association."