Fenofibrate - First Lipid Modifying Agent Shown to Protect Diabetic Eye

Fenofibrate - First Lipid Modifying Agent Shown to Protect Diabetic Eye

November 06, 2007

    SYDNEY, Australia, Nov. 6 /Xinhua-PRNewswire/ -- 

     - First Lipid Modifying Agent Shown to Reduce Risk of
Leading Causes of  
       Blindness and Deteriorating Vision in Patients With
Type 2 Diabetes

     - Reduces Need for Laser Treatment in Patients With
and Without Known 
       Diabetic Retinopathy

     - Significantly Decreases Progression of Diabetic Eye
Disease

    Fenofibrate is the first and only widely available
lipid modifying agent to demonstrate significant protection
to the eye of patients with type 2 diabetes, reducing the
need for laser therapy in a wide spectrum of patients which
should decrease the risk of progressive loss of vision.

    These effects appear independent from blood glucose as
well as baseline lipid levels, and are not explained by
blood pressure values.

    These important, new results are published online in
the Lancet today by investigators from the Fenofibrate
Intervention and Event Lowering in Diabetes (FIELD) Study.

    Analyses of the results show that fenofibrate:

    - Significantly reduces the requirement for a first
laser treatment for
      diabetic eye disease:

    - 31 per cent overall (p = 0.0002)

    - 31 per cent (p = 0.002) for maculopathy, a major
cause of blindness

    - 30 per cent for proliferative retinopathy (p=0.015).

    - Significantly decreases the total number of laser
therapies by 37 
      percent (p = 0.0003).

    Additionally, fenofibrate almost halved (49 per cent,
p=0.0002) the need for laser therapies in patients who were
not known to have diabetic eye disease at study entry when
considering all courses of laser therapy.

    These protective effects appear to begin after only
eight months of treatment and increase throughout the
five-year treatment period.

    Fenofibrate also demonstrated, in a sub-study, a
significant reduction in the progression of eye disease
with a:

    - 34 per cent reduction in a combined exploratory
endpoint (progression
      of retinopathy grading by 2 steps, development of
macular oedema and one 
      or more laser treatments, 16.1% vs. 11.1% - HR 0.66,
95% CI 0.47-0.94; 
      p=0.022).
    - Reduction by 79 per cent of the progression of
existing retinopathy (14
      cases with placebo, 14.6% vs. 3 cases with
fenofibrate, 3.1% p=0.004).
    - Several other endpoints did not differ significantly
between groups
      such as the occurrence of new retinopathy, of hard
exudates or worsening  
      in visual acuity.

    These new results from the FIELD trial conducted in
Australia, New Zealand and Finland, come from an analysis
of the reasons for the reduction in laser therapy reported
in the initial FIELD publication and a pre-specified
ophthalmology sub-study of the effect of fenofibrate on the
progression of diabetic retinopathy in 1,012 patients who
had repeated eye examinations.

    Lead investigator of FIELD, Professor Anthony Keech of
the NHMRC Clinical Trials Centre, University of Sydney,
Australia, said: "For the first time we have shown
that a widely available lipid modifying agent, fenofibrate,
reduces the complications of diabetic eye disease -- the
major cause of impaired vision in adults in the
industrialised world."

    "Importantly, the study also demonstrates that
patients without prior known diabetic eye disease (but
probably already at early stage of retinopathy) gain
significantly from fenofibrate.

    "In this group the subsequent need for total laser
therapy was almost halved. Therefore, we can now hope that
we can intervene to significantly reduce the progression of
retinopathy before it requires laser treatment."

    Importance for millions of diabetics

    Eye disease, including diabetic retinopathy and macular
oedema, affects up to 50 million of the 200 million people
with diabetes worldwide, as after about 10 years of
diabetes most patients will experience clinically
significant changes in their vision.

    Even with intensive multifactorial therapy
(antihypertensive agents, oral antidiabetic agents,
statins) retinopathy either developed or progressed in
about half of patients with type 2 diabetes within eight
years (STENO 2 study).

    Moreover, beyond control of blood pressure and blood
glucose, no effective treatment is widely available,
according to another FIELD investigator, Professor Paul
Mitchell of Westmead Hospital, Sydney, Australia.

    He said: "We have to rely on laser treatment which
is only partially effective and can result in diminished
visual field and other adverse effects. Additionally,
access to laser treatment is limited in many countries.
Therefore, these results offer an important new treatment
option to protect the eye of many patients with type 2
diabetes."

    Other clinical benefits

    Additional results from the FIELD Study reported this
week at the Scientific Sessions of the American Heart
Association in Orlando, show that fenofibrate significantly
decreased the risk of non-traumatic amputations by 38 per
cent (p = 0.011). Meanwhile, earlier data demonstrated that
fenofibrate also significantly reduces microalbuminuria, a
marker of the risk of progressive renal disease.

    In addition to these microvascular benefits, new data
presented at the AHA 2007 demonstrate that fenofibrate
reduced total CVD events by 26 per cent in diabetic
patients with elevated triglycerides (> 2.26mmol/L) and
low HDL-cholesterol ( < 1 mmol/L for men and < 1.3
mmol/L for women).

    Discussing the implications of these new results,
Professor Keech said: "The microvascular benefits of
fenofibrate -- in the eye, the limbs and the kidney --
combined with the reduction in overall cardiovascular
events, means that fenofibrate offers an important
opportunity to protect patients from the most serious
consequences of type 2 diabetes.

    The FIELD study and the detailed examinations in the
sub-study represent the largest randomised trial database
addressing the effects of a fibrate on diabetic retinopathy
and its treatment. The protective effects on the eye alone
are enough to support its consideration for many patients
but the determination of the stage of the disease as to
when to intervene should be considered exploratory."

    Notes to editors

    About the study

    The Fenofibrate Intervention and Event Lowering in
Diabetes (FIELD) study was conducted in 9795 patients aged
50-75 from Australia, New Zealand and Finland with type 2
diabetes. In addition a sub-study was conducted in 1,012 to
evaluate the development of diabetic retinopathy and the
symptoms of eye disease. The study was supported by the
manufacturer of fenofibrate, Laboratoires Fournier SA, part
of the Solvay Group: FIELD was designed, conducted and
analysed independently of the sponsor by the FIELD study
investigators, and coordinated by the NHMRC Clinical Trials
Centre, University of Sydney. Fenofibrate is marketed
world-wide by Solvay Pharmaceuticals and Abbott USA.
Results of the latest study are published on-line in the
Lancet ( http://www.thelancet.com/journals/eop ).

    The absolute risk reductions in first laser treatment
were:

    - Overall 1.5 per cent
    - Maculopathy 1.0 per cent
    - Proliferative retinopathy 0.7 per cent.

    About diabetic eye disease

    Diabetes-related eye disease is common and if untreated
or poorly treated leads to deterioration of vision and
ultimately blindness. It occurs when the small vessels
(microvasculature) of the eye are damaged by the
consequences of diabetes such as increased glucose and
raised blood pressure. Research also suggests other
critically important factors such as inflammation of the
small vessels of the eye which significantly increase the
risk of damage to the retina.

    What are diabetic retinopathy and macular oedema?

    Diabetic retinopathy arises from changes in the blood
vessels of the retina, a nerve layer behind the eye that
senses light. When these blood vessels become damaged,
vision loss occurs by two processes known as
"proliferative retinopathy" and "macular
oedema". Proliferative retinopathy occurs when new
vessels bleed into the centre of the eye often resulting in
blurred vision. Macular oedema occurs when fluid leaks from
these blood vessels into the centre of the retina or
macula, making it difficult to focus. Both of these
conditions may eventually destroy the retina if left
untreated. While laser therapy is a successful treatment in
preventing blindness, it may result in the loss of vision
when the macula is already involved.






    For more information, or to arrange an interview,
please contact: 

    Australia:
     Justin O'Day, Ophthalmologist, Peter Colman
     Diabetologist, Tim Davis, Diabetologist
     Via: Beth Quinlivan, University of Sydney
     Tel:    [phone]
     Mobile: [phone]

    At the AHA Conference
     Orlando Florida, Anthony Keech, Study Chairman
     Paul Mitchell, Ophthalmologist
     Via: Olivia Rajabaly, Euro RSCG Life
     Tel:    [phone]
     Mobile: [phone]