From the 67th annual scientific sessions of the American Diabetes Association: Lipid-lowering therapies reduce development of peripheral neuropathy


Statins and fibrates reduce the risk of peripheral neuropathy in patients with type 2 diabetes independent of the agents' effects on lipids, according to results presented at the 67th annual scientific sessions of the American Diabetes Association.

Key Points

The analysis involved 1,294 patients with type 2 diabetes who were enrolled in the Fremantle Diabetes Study between 1993 and 1996 and included a longitudinal subset of 531 patients with type 2 diabetes.

Patients were assessed for neuropathy at baseline using the clinical portion of the Michigan Neuropathy Screening Instrument; 30.9% of the 1,294 patients with type 2 diabetes had peripheral neuropathy; 136 patients in the subset had neuropathy. Multiple regression analysis and a Cox proportional hazards model were performed. Because of increased use of statins (7.6% at baseline and 34.9% at 5 y) and fibrates (6.1% at baseline and 8.9% at 5 y) during follow-up, these therapies were considered for entry into the Cox model as time-dependent covariates.

According to Dr Davis, the data suggest that statins and fibrates work to prevent neuropathy through different mechanisms. He said the use of both drugs may produce greater benefit than either drug used alone.

These results are consistent with those from the Fenofibrate and Event-Lowering in Diabetes (FIELD) study and contradict early case reports that statin use may produce neuropathy.

In the FIELD study, the use of fenofibrate was associated with an approximate 30% improvement in laser-treated retinopathy and a significant reduction in the incidence of microalbuminuria compared with placebo, suggesting microvascular benefits of lipid-lowering therapy, Dr Davis said.

"Because we didn't find any association between lipid parameters and neuropathy at baseline, we postulate that the benefit of lipid-lowering therapy is independent of lipid parameters measured biochemically," Dr Davis said.

In both studies, the lack of a current clinical indication for statin or fibrate drugs to be used for preventing diabetic microangiopathy "strengthens the case for an association between lipid-lowering therapy and prevention of these complications because there's no allocation bias in our sample," Dr Davis said.

According to Dr Davis, the reduction in the development of peripheral neuropathy is probably a class effect of statins and fibrates. The statins used at the start of the trial (1993) were atorvastatin, simvastatin, and pravastatin; patients who received fibrates were assigned to gemfibrozil. At the end of the longitudinal study, the majority of patients receiving fibrates were treated with gemfibrozil, although some patients received fenofibrate; the majority of patients in the statin group received atorvastatin, followed by simvastatin and pravastatin.

Dr Davis said that because this was an observational study, caution must be used when interpreting the results, but that the relative risk reduction for neuropathy is similar to that demonstrated with the use of statins for the prevention of myocardial infarction (MI).

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