Authors:  Rajamani,K.;Donoghoe,M.;Li,L.;Ting,R. -D;Colman,P.;Scott,R.;Laakso,M.;Keech,A.

Publication: Atherosclerosis Supplements

Year: 2010

Volume: 11

Issue: 2

Start Page: 219

ABSTRACT:

Introduction: Peripheral neuropathy, a microvascular complication of diabetes, is a major contributor to lower limb ulcer formation and amputation and their devastating consequences. The aim of this analysis was to evaluate the effect of the lipid-modifying drug, fenofibrate, on neuropathy.

Methods: 9795 patients with type 2 diabetes mellitus were randomised to receive fenofibrate 200 mg/day or matching placebo for 5 years. The presence of neuropathy symptoms was recorded at baseline and sensation tested using a standard monofilament technique, repeated at 2 years and study close. All nontraumatic lower limb amputations were recorded, and classified as major or minor.

Results: 5.8% of participants (564 of 9795) had documented monofilament neuropathy at baseline. By study close, neuropathy had increased to 8.0% of placebo patients, compared with 6.6% of those receiving fenofibrate (between-group difference, adjusted for baseline, P = 0.02). This reflected an 18% reduction in new neuropathy (5.3% vs 4.4%; OR 0.82, 95%CI 0.67-1.01, P = 0.06), and a 40% greater reversal of baseline neuropathy with treatment (42% vs 55%; OR 0.60, 95%CI 0.42-0.88, P = 0.009). Neuropathy was one of the strongest predictors of amputation, increasing the risk of a first amputation approximately threefold (HR 2.7, 95% CI 1.8-4.1; P < 0.001) and a minor amputation even more.

Conclusions: Long-term use of fenofibrate reduced overall neuropathy and increased the reversal of pre-existing neuropathy in type 2 diabetes, although the mechanisms remain unknown. These benefits are likely to partly explain the large 37% reduction seen in the risk of total amputations with fenofibrate in the FIELD study.

• Listing ID: 4565
• Author/s: Rajamani,K.;Donoghoe,M.;Li,L.;Ting,R. -D;Colman,P.;Scott,R.;Laakso,M.;Keech,A.
• Publication: Atherosclerosis Supplements
• Year: 2010
• Volume: 11
• Issue: 2
• Start Page: 219
• Article Keywords: fenofibrate;placebo;lipid;diabetes mellitus;peripheral neuropathy;neuropathy;amputation;risk;patient;sensation;leg amputation;leg;ulcerogenesis;non insulin dependent diabetes mellitus;field study