Fenofibrate reduces diabetic amputation risk

Medical Tribune November 2008 P7
David Brill

Fenofibrate treatment can reduce the risk of amputations among type 2 diabetics, recent data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study show.

Patients who took the drug had a 38 percent risk reduction for all first amputations, after an average of 5 years of follow-up (P=0.011).

The effect was particularly marked for amputations related to microvascular disease, with a 47 percent risk reduction for this endpoint (P=0.025).

“In all subjects with diabetes fenofibrate should be considered as add-on therapy for both macrovascular and microvascular outcomes,” said Professor Anthony Keech, principal investigator for the FIELD study, who presented the latest results at a press conference.

“It is the only lipid-modifying agent which has been shown to reduce the microvascular complications of diabetes and as such it represents a major breakthrough in diabetes care. And the great news is that it turns out fortuitously that statins and fenofibrate can be given safely in combination, which is not necessarily true of other fibrates,” he said.

Previous reports from the FIELD trial have shown that fenofibrate has beneficial effects on the incidence of cardiovascular events, progression of albuminuria and the development of diabetic retinopathy. [Lancet 2005 Nov 26;366:1849-61; Lancet 2007 Nov 17;370:1687-9]

The study randomized 9,975 patients aged 50 – 75 with type 2 diabetes to either placebo or fenofibrate (200 mg/day).

All amputations that occurred over the study period were assessed by two clinicians who were blinded to treatment. Amputees were more likely to be male and a smoker, and to have a higher systolic blood pressure, a longer duration of diabetes, and a history of vascular disease.

The new data also revealed a 23 percent risk reduction for macrovascular disease-related amputations alone but this was not statistically significant (P=0.26).

Dr. Alberto Zambon, a lipoproteins and atherosclerosis expert from the University of Padua, Italy, said that data from the Steno study show that the majority of diabetic patients experience progression of microvascular disease even when receiving a multifactorial approach involving statins and control of glucose and blood pressure. [N Engl J Med 2003 Jan 30;348(5):383-93]

“Adding fenofibrate to the current optimal standard of care will lead to a further reduction of the excess risk we see in these patients as far as diabetic retinopathy and peripheral neuropathy are concerned,” he said.

He added that fibrates can bring benefits above and beyond those of statins as they modulate gene expression whereas statins interact with the metabolic pathways of cholesterol production.

Keech, a professor of medicine, cardiology and epidemiology at the University of Sydney, Australia, said that the amputation risk in diabetics is around 25 to 30 times higher than in non-diabetics.

“In some studies the risk of death within 5 years of the first amputation is as high as 70 percent so they really are bad news, reflecting severe vascular damage through the diabetes process,” he said.

“So the fact that overall amputations were reduced by 38 percent by fenofibrate, in the setting of angiotension-converting enzyme inhibitors and statin use, blood pressure control and excellent glycemic control, is a major advance.”