New Drug Shows Significant Gain for Diabetic Retinopathy
By paddy Kamen
The debilitating vision loss associated with Type 2 Diabetes has been dealt a significant blow, according to an international study.
Diabetes is a chronic disease that occurs when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. Hyperglycaemia, or raised blood sugar, is a common effect of uncontrolled diabetes and over time leads to serious damage to many of the body’s systems, especially the nerves and blood vessels. 1
Diabetes comes in two types: Type 1 diabetes results from cellular-mediated autoimmune destruction of pancreatic islet β-cells causing the loss of insulin production. It ranks as the most common chronic childhood disease in developed nations 2. Type 2 diabetes is often, but not always, associated with obesity, which itself can cause insulin resistance and lead to elevated blood sugar levels 3.
Type 2 diabetes (T2D) is a dangerous and insidious disease: because the onset is slow, many people don’t know they have it and by the time they are diagnosed, up to half of them already have macrovascular and microvascular complications.
The diagnosis of T2D usually occurs after age 40, although the age of onset is often a decade earlier in populations with a high diabetes prevalence. Increasingly, however, T2D is being reported in children from both the developed countries like Canada and underdeveloped countries like Bangladesh. T2D constitutes about 85-to-95 per cent of all diabetes in developed countries, and accounts for an even higher percentage in developing countries. Its incidence is increasing far more quickly than that of type 1 diabetes 4.
246 million people worldwide had diabetes in 2007 5. It is the fourth or fifth leading cause of death in most developed countries and there is substantial evidence that T2D is epidemic in many developing and newly industrialized nations 6.
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 pathophysiologic processes related to 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 risk of damage to the retina.
Diabetic retinopathy arises from changes in the blood vessels of the retina. 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.
Eye disease, including proliferative retinopathy and macular oedema, affects up to 50 million of those with diabetes worldwide. After approximately 10 years of diabetes, most patients will experience clinically significant changes in their vision. Moreover, beyond control of blood pressure and blood glucose, no effective treatment is widely available, according to FIELD investigator, Professor Paul Mitchell of Westmead Hospital, Sydney, Australia. “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.”
The FIELD Study
The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study 7 was conducted in 9795 patients aged 50-75 from Australia, New Zealand and Finland with T2D. In addition a sub-study was conducted with 1,012 patients, and a FIELD sub-analysis examined the occurrence of laser treatment for retinopathy. The results were published in The Lancet in November 2007 8 .
The study’s findings offer real hope for people with T2D, demonstrating that fenofibrate reduces the requirement for a first laser treatment for diabetic retinopathy by 31 per cent overall. The drug also decreases the total number of laser therapies by 37 per cent.
The protective effects of the medication appear to begin after only eight months of treatment and increase throughout the five-year treatment period.
Fenofibrate also demonstrated a 79 percent reduction in the progression of existing retinopathy.
Lead investigator of FIELD, Professor Anthony Keech of the NHMRC Clinical Trials Centre, University of Sydney, notes, “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 industrialized 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.”
The FIELD study and the detailed examinations in the sub-study represent the largest randomized trial database addressing the effects of a lipid modifying agent, fenofibrate, 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,” says Dr. Keech.
Additional results from the FIELD Study reported at the Scientific Sessions of the American Heart Association 2007 9 show that fenofibrate significantly decreased the risk of non-traumatic amputations by 38 per cent. 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 cardiovascular disease events by 26 per cent in diabetic patients with elevated triglycerides and low HDL-cholesterol.
Discussing the implications of these new results, Professor Keech observed: “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.”
Fenofibrate, from Solvay Pharma Inc. is sold in Canada under the name Lipidil EZ® 10.
*With notes from the FIELD study website: http://www.fieldstudy.info/investigators/index.asp
1 http://www.who.int/diabetes/en/
2 LaPorte R, Matsushima M, Chang Y. Prevalence and incidence of insulin-dependent diabetes. In Diabetes in America, second edition, ed. NDDG NIH 1995:37-46.
3 www.eatlas.idf.org (accessed July 2007).
4 Fagot-Campagna, A. Emergence of type 2 diabetes mellitus in children: epidemiological evidence. Journal of Pediatric Endocrinology and Metabolism 2000;13:1395-402.
5 www.eatlas.idf.org (accessed July 2007).
6 World Health Organization. Diabetes: the cost of diabetes. Fact sheet N°236. September 2002.
7 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.
8 www.thelancet.com. Published online November 6,2007 DOI:10:1016/SO140-6736(07)61607-9
9 http://circ.ahajournals.org/cgi/search?fulltext=Fenofibrate&volume=
116&issue=16+Supplement&flag=MTMTG_ABSTRACT_ARTICLE&
journalcode=circulationaha
10 Lipidil EZ® is a registered trademark of Fournier Industrie et Santé; Licenced use by Fournier Pharma Inc. Montréal, QC, H3B 1P9. Solvay Pharma Inc. is acting as the authorized agent for Fournier Pharma Inc. until the legal amalgamation of Solvay and Fournier has been completed.
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