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CTC, University of Sydney

Fenofibrate Reduces the Risk of Amputations in Patients With Type 2 Diabetes

Rome (ots/PRNewswire)

  • Exciting New Data From the FIELD Study Show Additional Microvascular-Associated Benefits of Fenofibrate
  • The First Time in a Large-Scale Prospective Study That any Lipid-Modifying Therapy has Been Shown to Significantly Reduce the Risk of Lower-Limb Amputation in Patients With Type 2 Diabetes
Fenofibrate treatment in people with type 2 diabetes mellitus
reduces the risk of amputations, including those associated with
microvascular disease, according to new data from the FIELD study
presented for the first time at the European Association for the
Study of Diabetes, Rome, September 2008.(1) These findings add to
other microvascular benefits demonstrated with fenofibrate in
diabetic retinopathy, published in The Lancet 2007,(2) and diabetic
nephropathy, published in The Lancet 2005.(3)
The FIELD study researchers showed that, over an average
follow-up of 5 years, treatment with fenofibrate reduced the risk of
non-traumatic amputation by 38% (p=0.011), mainly due to a reduction
in amputation considered related to microvascular disease by 47%
(p=0.025). Patients who had an amputation associated with
microvascular disease were slightly younger and heavier and were more
likely to have other microvascular disease, including diabetic eye
and kidney disease.
According to Professor Keech, lead investigator of the FIELD
study: "The effects of fenofibrate in reducing the risk of
amputations in patients with established microvascular complications
were particularly striking, and further support the important
clinical benefits of fenofibrate on microvascular associated events
in type 2 diabetes."
The FIELD analysis on amputations
All non-traumatic amputations that occurred during the FIELD
study were reviewed by 2 clinicians blinded to study treatment.
Reasons for amputation were recorded as presumed microvascular
(amputations of toes or forefoot (called "minor" amputations),
without embolism or existing large artery disease in the limb) or
macrovascular (all other "minor" and all below-knee and above-knee
("major") amputations).
The profile of patients more likely to require amputation was:
    - Male
    - Longer duration of diabetes
    - Higher systolic blood pressure
    - Current smoker
    - Previous vascular disease
    - More microvascular complications
    - More insulin use at baseline
All these characteristics were considerably more common than in
patients who did not undergo amputation.
Among all patients with an amputation, the profile of patients
with a microvascular-associated complication was:
- Slightly younger (p=0.03)
    - Heavier (p<0.001)
    - Slightly higher HbA1c (p=0.07)
    - More other microvascular complications (p=0.002)
Significance for millions of type 2 diabetes patients
Peripheral neuropathy (nerve damage) is a serious complication of
diabetes. Recent data indicate that one in 5 people with diabetes
(20%) have peripheral neuropathy, irrespective of whether diabetes
has been clinically diagnosed. The risk for peripheral neuropathy is
about 2-fold higher than in people without diabetes.(4) The
combination of peripheral neuropathy with problems associated with
the blood supply to the feet can lead to foot ulcers and slow-healing
wounds. Infection of these wounds can result in amputation. Every 30
seconds a limb is lost to diabetes and 40-70% of all lower  extremity
amputations are related to diabetes.(5)
Evidence indicates that improvements in management, specifically
drug therapy, have contributed to a decline in cardiovascular
mortality in patients with diabetes.(6) As people with diabetes live
longer, they are more likely to experience microvascular
complications of diabetes. Together with the increasing prevalence of
type 2 diabetes among an ageing population,(7) the burden of
microvascular complications, including diabetic neuropathy and
amputation, is expected to increase substantially in the future.
Even when treated in accordance with current standards for
diabetes care, patients remain at high residual risk of vascular
complications. This is highlighted by evidence from the STENO-2 trial
in patients with type 2 diabetes. Despite optimal control of
LDL-cholesterol and diastolic blood pressure and fair glycaemic and
systolic blood pressure control, microvascular disease such as
diabetic retinopathy, nephropathy or neuropathy developed or
progressed in up to 50% of these patients within 8 years.(8)
Fenofibrate reduces the total cardiovascular risk in patients
with type 2 diabetes and atherogenic dyslipidaemia (elevated
triglycerides and low HDL-cholesterol)
While current management strategies aimed at lowering LDL
cholesterol with statin therapy are effective in reducing
cardiovascular risk in patients with diabetes, supported by extensive
evidence from a large number of well-controlled studies,(9) there are
also clear limitations to statin treatment. Even at optimal statin
doses, extensive evidence from large clinical trials show that 65-90%
of CVD events in diabetes patients are not prevented with statin
therapy.(9) This is largely because statins only partly address the
abnormalities of low HDL-cholesterol and elevated triglycerides which
are common in patients with type 2 diabetes. It is important to note
that triglyceride and HDL-cholesterol levels are strong predictors of
cardiovascular events, even in patients achieving LDL-cholesterol
levels below 1.8mmol/L (70mg/dL)
Additional FIELD data presented at this year's EASD highlight
that cardiovascular risk reduction with fenofibrate treatment is
greatest in patients with type 2 diabetes with atherogenic
dyslipidaemia (the combination of elevated triglycerides
(>2.3mmmol/L) plus low high-density lipoprotein [HDL] cholesterol
(<1.0mmol/L for men and <1.3mmol/L for women); fenofibrate treatment
showed a 27% reduction in CVD risk in these patients.(10) The FIELD
study investigators showed that in patients with marked diabetic
dyslipidemia, 23 patients have to be treated with fenofibrate for 5
years to avoid one CV event (NNT = 23), which is comparable with the
benefits of statin therapy already shown in landmark trials.
These new data highlight the benefits of fenofibrate on
amputations, including microvascular-associated amputations.
Together, with previously published data showing benefits for the eye
and the kidney, these results highlight the urgent need to address
residual vascular risk in patients with type 2 diabetes.
Note to Editors
A complete version of this release including all reference
information  can be found at:
http://www.prnewswire.co.uk/cgi/news/release?id=236272

Contact:

For more information, or to arrange an interview, please contact:
Australia: James Best, Diabetologist, Russell Scott, Diabetologist,
Michael d'Emden, Diabetologist, Via: Beth Quinlivan, University of
Sydney, Ph: +61-2-9036-65-28, Mob: +61-0-419-229-134; At EASD, Rome,
Italy, Peter Colman, Diabetologist, Richard O'Brien, Diabetologist,
Anthony Keech, Study Chairman, Via: Wendy Gerber, MS&L, Ph:
+44-20-7878-3259, Mob: +44-7949-034-007