Treatment of patients with Type 2 diabetes without known large-vessel disease with fenofibrate significantly reduces their risk for amputation events, report researchers from the FIELD study.

However, the risk for major amputation among patients with atherosclerotic disease of the major peripheral arteries was not significantly influenced by fenofibrate treatment.

“Amputations in people with Type 2 diabetes mellitus substantially impair their quality of life and impose high costs on health-care systems,” say Kushwin Rajamani (University of Sydney, New South Wales, Australia) and co-investigators.

The researchers tested the effect of fenofibrate on amputation risk in participants of the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study, which included 9795 patients with Type 2 diabetes aged 50??”75 years.

Of these, 4895 were randomly assigned to take fenofibrate 200 mg/day and 4900 to take placebo for a period of 5 years. During this time, 115 patients had one or more non-traumatic lower-limb amputations as a result of their diabetes.

Major amputations were defined as those above and minor those below the ankle. The researchers further classified individuals who underwent amputation as having minor amputation without previous large-vessel disease - thought to be due to microvascular disease, or minor or major amputations with documented large-vessel disease ??” thought to be due to atherosclerotic disease of the major peripheral arteries.

Writing in The Lancet, the authors report that fenofibrate treatment significantly reduced the risk for first on-study amputation (all types) and minor amputation without previous large-vessel disease by 36% and 47%, respectively, compared with placebo.

However, the reduction in risk for major amputation events with documented large-vessel disease was non-significantly different between the fenofibrate- and placebo-treated groups (7% reduction).

“These findings could lead to a change in standard treatment for the prevention of diabetes-related lower-limb amputations,” conclude Rajamani et al.

Of note, the reduction in amputation risk observed in this study was not associated with any lipid variables, suggesting “the effects of treatment with fenofibrate on the risk of amputation might go beyond the improvements in controlling the lipid profile,” says the team.

“Because development and care of skin ulcers are formidable predictors of future amputations, one has to wonder whether some of the effects of fenofibrate can be attributed to improvement in wound healing,” commented Sergio Fazio and MacRae Linton (Vanderbilt University Medical Center, Nashville, Tennessee, USA) in an accompanying commentary.

“This effect ??” more so than anti-inflammatory, antioxidant, or endothelium-mediated effects ??” would set fibrates apart from the many agents (statins, antihypertensives, aspirin, and vitamin E) that have so far been unable to reduce amputations in people with diabetes.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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