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Fenofibrate may reduce amputations in diabetics

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – Treatment with fenofibrate can reduce the risk of amputation in people with type 2 diabetes by 36%, according to a report in the May 23rd issue of The Lancet.

The effect, which is probably mediated through non-lipid mechanisms, was largely confined to minor amputations in patients without known large-vessel disease, the report indicates.

Diabetes is the number one cause of non-traumatic lower-extremity amputations in developed countries, Dr. Kushwin Rajamani, from the University of Sydney, Australia, and co-researchers note. Roughly one in ten patients with diabetes will require at least one amputation during their lifetime. Moreover, prior research has suggested that control of glucose levels and blood pressure as well as reduction of cholesterol levels does not prevent the risk of amputation.

In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, the goal was to determine if long-term treatment with fenofibrate could reduce the incidence of micro- and macrovascular complications, including amputations, in type 2 diabetics. In an earlier study, Dr. Rajamani’s team had shown that fenofibrate therapy had a beneficial effect on diabetic retinopathy that was unlikely to be related to its lipid-lowering effect.

The FIELD study featured 9795 patients, 50 to 75 years of age, who were randomized to receive fenofibrate 200 mg or placebo daily for 5 years.

During follow-up, 115 patients required a lower-limb amputation due to diabetes. Correlates of amputation included prior cardiovascular disease, microvascular disease, prior non-traumatic amputation or skin ulcer, smoking and longer diabetes duration, the report indicates.

As noted, fenofibrate therapy reduced the risk of a first amputation by 36% (p = 0.02). Further analysis showed that this treatment reduced the risk of minor amputation in patients without known large-vessel disease by 47% (p = 0.027), but had no significant effect on the risk of major amputations.

Although the lipid levels of amputation patients differed from those of non-amputation patients, the magnitude was small, the researchers note.

According to an accompanying editorial, the beneficial effect seen with fenofibrate may stem from an enhancement in healing of skin ulcers.

Prior research has shown that fibrates promote keratinocyte differentiation and augment the epidermal barrier, Dr. Sergio Fazio and Dr. MacRae F. Linton, from Vanderbilt University Medical Center, Nashville, comment. “This effect — more so than anti-inflammatory, antioxidant, or endothelium-mediated effects — would set fibrates apart form the many agents (statins, antihypertensives, aspirin, and vitamin E) that have so far been unable to reduce amputations in people with diabetes.”

Reference:
Lancet 2009;373:1740-1741,1780-1788.