May 21, 2009 -- Treating type 2 diabetes patients with a cholesterol-lowering drug called fenofibrate cuts the risk of a first diabetes-related limb amputation by 36%, according to a new study published this week in The Lancet.
"I would call that a substantial reduction in risk," says James Best, MD, professor of medicine at the University of Melbourne in Australia and a co-author of the study.
The reduction in limb amputation risk is probably not directly related to the cholesterol-lowering effects of the drug, he tells WebMD, but rather to some of the other effects, such as improving the functioning of small blood vessels.
Amputation & Type 2 Diabetes: Background
People with diabetes are more likely than people without the condition to have a foot or leg amputation, according to the American Diabetes Association.
That's because people with diabetes are likely to have peripheral artery disease, reducing blood flow to the lower legs and feet, and to have nerve disease called diabetic neuropathy, boosting their risk of getting ulcers and infections that can result in a need for amputation.
Fenofibrate & Amputation Risk: Study Details
Best and his colleagues looked at 9,795 patients in Australia, New Zealand, and Finland with type 2 diabetes, aged 50 to 75, who had taken part in the FIELD study (Fenofibrate Intervention and Event Lowering in Diabetes). The patients were assigned to get either fenofibrate at a dose of 200 milligrams a day or placebo for five years.
FIELD is a clinical trial that previously analyzed the drug's effect on heart disease death and nonfatal heart attack and showed it did not have a significant effect on those outcomes, but it did help with other problems, such as reducing risk of diabetic retinopathy, a diabetes-related eye problem.
Among the funding sources were Laboratoires Fournier SA, now part of Solvay Pharmaceuticals, which markets fenofibrate, and the National Health and Medical Research Council of Australia.
The researchers got information on amputation and whether they were minor, defined as below the ankle, or major, defined as above the ankle.
They also assessed whether large blood vessel disease or small blood vessel disease was found in the amputated limb.
Fenofibrate & Amputation Risk: Study Results
Over the course of the study, 115 patients had amputations of the lower limbs related to their diabetes. The researchers also found:
- Overall, the risk of first amputation was 36% lower for all patients given fenofibrate compared to those given placebo. Although 70 of those on placebo had amputation, 45 of those on the drug did.
- The risk of minor amputation in patients who did not have large vessel disease was even lower, 47%, for those who took the drug compared to those who got the placebo.
- Risks didn't differ significantly between groups for major amputations.
- Height predicted risk of amputation. For every 4-inch increase in height, there was a 1.6-times boost in risk. (Best notes that this is not a new finding.)
Fenofibrate & Amputation: Take-Home Message
Best puts the study findings in perspective this way. "What we have to keep in mind is that amputation is not as common as heart attack [among those with type 2 diabetes]." Although the effect of the drug on amputation risk was significant, he says, "This doesn't mean everyone with diabetes should start taking fenofibrate to prevent amputation. The therapy should be targeted to those at high risk for amputation."
That includes those who have nerve damage in their feet from their diabetes, who have an ulcer on their foot, or who have had a previous amputation, Best says.
Fenofibrate & Amputation: Second Opinions
"It's an interesting study that may change some people's approach [to diabetes treatment]," says Richard Jackson, MD, senior physician at Joslin Diabetes Center and assistant professor of medicine at Harvard Medical School, Boston, who occasionally does prescribe the drug, typically to bring down high triglyceride levels.
But he adds a caveat. "The medication could be helpful, but it's only one study." More studies are needed, he says.
Another expert who reviewed the study findings for WebMD agrees. "We need to do a larger trial to understand its mechanism and confirm the findings," says Richard M. Bergenstal, MD, president-elect of the American Diabetes Association and executive director of the International Diabetes Center at Park Nicollet Health Services in Minneapolis.
Meanwhile, he says, the study results point to the importance of preventive care. The researchers found that the strongest predictors of a first amputation included a history of previous amputation or diabetic skin ulcers, nerve problem, or a history of peripheral vascular disease. "Anybody who has neuropathy and a history of amputation or ulcer, we need to follow them very closely because they are at higher risk."