Tuesday, June 21, 2011

Diabetes Risk Rises as Statin Dose Increases

By: MARY ANN MOON, Internal Medicine News Digital Network

The risk of developing type 2 diabetes rises with increasing doses of statin therapy, according to the findings of a large meta-analysis in the June 22/29 issue of JAMA.

"Our findings suggest that clinicians should be vigilant for the development of diabetes in patients receiving intensive statin therapy," said Dr. David Preiss of the BHF Glasgow (Scotland) Cardiovascular Research Centre at the University of Glasgow, and his associates.

Several recent studies have suggested that statin therapy may raise the risk of diabetes, and some have indicated that the risk is higher at higher doses of the drugs.

Dr. Preiss and his colleagues conducted a meta-analysis of five large (at least 1,000 subjects each) randomized clinical trials that compared moderate-dose with intensive-dose statin therapy and followed patients for a minimum of 1 year. These trials were intended to compare cardiovascular outcomes, but they also tracked adverse events, blood glucose levels, and the use of diabetes medications, so cases of new-onset diabetes could be identified.

Overall, 32,752 subjects who did not have diabetes at baseline were followed for a mean of 5 years. During that time 2,749 subjects (8%) developed diabetes.
There were 149 more cases of diabetes among subjects taking intensive statin therapy than in those taking moderate statin therapy, for an odds ratio of 1.1.

"In absolute terms, there were two additional cases of diabetes per 1,000 patient-years among those receiving intensive-dose therapy (mean 18.9 cases per 1,000 patient-years with high-dose statin treatment vs. 16.9 cases per 1,000 patient-years with moderate-dose therapy), corresponding to a number needed to harm of 498 per year," the investigators said.

This dose-response relationship persisted across several subgroups of patients, regardless of age, HDL cholesterol level, body mass index, and fasting plasma glucose level at baseline. The dose-response relationship also was comparable between subjects receiving simvastatin and those receiving atorvastatin, Dr. Preiss and his associates said (JAMA 2011;305:2556-64).

However, more intensive statin therapy also provided clear cardiovascular benefits compared with less intensive statin therapy. "When expressed in absolute terms, there was one additional case of diabetes for every 498 patients treated for 1 year, compared with one fewer patient experiencing a cardiovascular event for every 155 patients treated for 1 year," they noted.

"We hypothesize that given that cardiovascular risk from diabetes is modest in the first decade after diagnosis, and as the benefit of statin therapy increases over time and in absolute terms with increasing age, net cardiovascular benefit in high-risk individuals will still strongly favor statin therapy," the investigators said.
The mechanism by which statins raise diabetes risk is not known. The data on subgroups in this meta-analysis do not shed light on the issue since all subgroups were at comparable risk.
Future research should examine "the impact of statin therapy on glycemic control, and treatment requirements in patients with established diabetes," they added.

Dr. Preiss’s associates reported ties to numerous industry sources.

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