Diabetes is by far the number one cause of blindness here in Saipan. \u00a0Diabetes can damage any part of the eye, but the most common way it leads to blindness is through the complication of diabetic retinopathy. \u00a0In the US mainland the National Institutes of Health (NIH) estimates that 28% of people with diabetes have retinopathy. \u00a0The problem in Saipan is much worse, over the last five years in our practice we have consistently seen that between 70-72% of our patients with diabetes have retinopathy.<\/p>\n
While treatments like laser photocoagulation and intravitreal injections such as avastin can prevent much of the most serious vision loss, they are only beneficial with more severe retinopathy.\u00a0 Until recently there has been no available medication to prevent the worsening of retinopathy to the severe stages. \u00a0Recent evidence has shown overwhelmingly that fenofibrate effectively reduces the worsening of mild to moderate retinopathy.<\/p>\n
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\u00a0<\/p>\n Fenofibrate first became available in the 1990\u2019s and has been used to treat elevated cholesterol and triglyceride levels. \u00a0Studies indicate that the beneficial effects seen for retinopathy are independent of any changes in the cholesterol levels. \u00a0The particular mechanism is not fully understood, but fenofibrate seems to protect against the breakdown of the blood-retinal barrier. \u00a0Numerous studies show that significant side effects are rare.<\/p>\n The first major study identifying a possible oral treatment for retinopathy was the Fenofibrate Intervention and Event Lowering in Diabetes \u00a0\u00a0the FIELD trial<\/a>\u00a0in 2009. \u00a0 9795 diabetes patients were randomized to fenofibrate or placebo for five years. \u00a0\u00a0The results were dramatic, the fenofibrate group was 79% less likely to have worsening retinopathy, and 31% less likely to need retinal laser surgery. \u00a0Both findings were highly significant.<\/p>\n The Action to Control Cardiovascular Risk in Diabetes,\u00a0ACCORD Lipid trial<\/a> which studied 5518 diabetes patients considered at high risk for cardiovascular disease, was released in 2010. \u00a0Patients were randomized to statin plus fenofibrate, or statin plus placebo.\u00a0 Simvastatin was used, the majority were at the maximal usual dose of 40 mg. \u00a0Again, dramatic results were seen. \u00a0The fenofibrate group showed \u00a036% less retinopathy progression, and was also 31% less likely to need laser surgery.<\/p>\n There are other results from these trials that have special interest in the CNMI.\u00a0 In the FIELD trial, the fenofibrate group had a significant 36% reduction in foot amputation.\u00a0 Both FIELD and ACCORD Lipid showed decreased risk of both micro and macroalbuminuria in the fenofibrate group. \u00a0Albuminuria is a test for protein in the urine. \u00a0Protein excretion in the urine is an early sign of kidney disease. \u00a0Decreasing this find<\/p>\n ing would likely decrease new cases of dialysis from diabetes. \u00a0There was also a non-significant trend towards less diabetic related dialysis in both trials for the fenofibrate group.<\/p>\n Following these studies there has been increasing talk of using fenofibrate to treat retinopathy.\u00a0 In 2013 Australia approved fenofibrate for retinopathy treatment.\u00a0 In December 2014 an editorial in the journal Ophthalmology<\/a> discussed this in great detail, see also this discussion in the\u00a0American Journal of Ophthalmology<\/a>\u00a0 \u00a0This summer I attended the Scientific Sessions of the American Diabetes Association.\u00a0 While there I listened as Emily Chew, the lead Ophthalmologist at the NIH presented as yet unpublished new findings showing the effectiveness of fenofibrate for retinopathy.<\/p>\n Kidney function is monitored when prescribing, as studies indicate fenofibrate should be stopped if GFR (a marker of kidney disease) goes below 30. \u00a0We also monitor liver enzymes, as this has been an issue in rare cases. \u00a0Fenofibrate is contraindicated in those with gallbladder disease, and has not been tested in pregnancy, so should be avoided in women of childbearing years. \u00a0It is relatively inexpensive, with an average US retail price under $30.00 per month, and is covered by every insurance in the CNMI. \u00a0 \u00a0An older, related medication gemfibrozil did have some significant side effects. \u00a0When combined with Statin medications it lead to an increased risk of a serious muscle condition called rhabdomyolysis. \u00a0The vast majority of studies have not shown this to be a concern with fenofibrate. \u00a0However, one study did show a possible link. \u00a0In that study there were 12.37 cases of rhabdomyolysis per 100,000 patient years of treatment, in other words it was rare. \u00a0Even though most studies do not show this link, caution is still warranted. \u00a0Patients taking fenofibrate should report muscle pain to their physicians right away.<\/p>\n In our clinic we take potential side effects very seriously. \u00a0We take careful precautions to avoid them whenever possible. \u00a0Also whenever concerns arise, we check with the best experts on medications, a Pharmacist. \u00a0 We are blessed in Saipan to have two very good pharmacies. \u00a0If you have any questions about diabetes or fenofibrate, please call me at 235-2030. \u00a0Further information is also available on our websight at hardteyeclinic.com<\/a>\u00a0 \u00a0I have been corresponding with one of our pharmacists about Fenofibrate. \u00a0I will share some of this correspondence below. \u00a0It goes into greater scientific detail than I usually will write in my blog, but I include it for those who might be interested.<\/p>\n \u00a0<\/p>\n Thank you so much for calling me the other day about fenofibrate, and the concerns it could lead to rhabdomyolysis when combined with statins, especially with higher statin dosage.\u00a0 We have been studying the use of fenofibrate to treat diabetic retinopathy carefully for about five years.\u00a0 I have attached to this email my \u201cdiabetes update\u201d I sent this out to the CNMI\u2019s physicians early last year, which briefly discussed this issue. \u00a0\u00a0As you know diabetic retinopathy is by far the leading cause of blindness here in the CNMI.\u00a0<\/em><\/p>\n Systemic drugs like fenofibrate, indicated primarily for cardiovascular disease and hyperlipidemia, have been considered the province of internal medicine practitioners.\u00a0 For this reason we have moved very slowly and cautiously before prescribing fenofibrate ourselves.\u00a0 We have had growing conviction, however, that many patients would benefit greatly from this therapy, so we have started prescribing.\u00a0 Each time we do, we send detailed reports to the primary care physician or nurse practitioner.<\/em><\/p>\n Like you stated in our phone call, there have been concerns about possible adverse events, especially when combining with statins.\u00a0 First regarding rhabdomyolysis.\u00a0 I discussed above that there was no indication of this combination increasing the risk in the major trials listed above (FIELD & ACCORD Lipid) in diabetes patients.\u00a0 A more general study was released in 2011.http:\/\/journals.sagepub. \u00a0<\/em><\/p>\n The next study was a meta-analysis of 12 studies published in 2016, again looking for increased risks when statins are combined w\/ fenofibrate. http:\/\/www.ijcem.com\/files\/ \u00a0<\/em><\/p>\n I read with interest the warnings on drugs.com<\/a> \u00a0https:\/\/www.drugs.com\/drug- \u00a0<\/em><\/p>\n While any indication of an increased risk of a condition as serious as rhabdomyolysis should be taken seriously, of course we must balance the risks with the potential rewards.\u00a0 If we ignore the benefits for albuminuria & limb amputation, the benefits in retinopathy progression in our opinion far outweigh the potential risks.\u00a0 We feel this is the case even if we only look at the one major study showing increased risk.\u00a0 Even in this study there were about 12 events per 100,000 patient years.\u00a0 We would have to balance this with the known prevention of worsening retinopathy in thousands of patients per case of rhabdomyolysis.\u00a0 The evidence is mixed, and in our opinion, overall points away from an increased risk for rhabdomyolysis in our treatment population.\u00a0 The studies specifically looking at diabetes patients showed no link.\u00a0 The meta-analysis of all available RCT\u2019s from 2013 and 2016, found no link.\u00a0 Again we could find no evidence from the literature of an increased risk of rhabdomyolysis and higher dosages of statin.\u00a0 See this discussion of the safety of combining fenofibrate with statins. \u00a0https:\/\/www.ncbi.nlm.nih.gov\/ \u00a0<\/em><\/p>\n While you specifically mention rhabdomyolysis in your call, I would also like to address another concern that has been raised.\u00a0 Citing the lack of evidence \u00a0of cardiovascular benefit in combining fenofibrate with statins, the FDA withdrew the approval of this combination for cardiovascular disease in April 2016. \u00a0http:\/\/www.medscape.com\/ \u00a0<\/em><\/p>\n Based on all of the above, we feel that in diabetes patients with mild to moderate diabetic retinopathy without contraindications (GFR below 30, elevated liver enzymes, gallbladder disease, and women of childbearing years), that fenofibrate will benefit our patients.\u00a0 This will be true whether or not they are also taking statin medication.\u00a0 Of course we are anxious to hear any and all evidence that would lead in a different direction as we all try to serve our mutual patients.<\/em><\/p>\n \u00a0<\/em><\/p>\n Thank you again for your help, and your service to our community.<\/em><\/p>\n![\"fundus](\"https:\/\/i0.wp.com\/saipandiabetesblog.com\/wp-content\/uploads\/2017\/03\/Diabetic-Retinopathy.jpg?resize=300%2C268\")
![\"Normal](\"https:\/\/i0.wp.com\/saipandiabetesblog.com\/wp-content\/uploads\/2017\/03\/Normal-retina.jpg?resize=300%2C268\")
<\/h2>\n
Evidence<\/h2>\n
The FIELD Trial<\/h3>\n
The ACCORD Lipid trial<\/h3>\n
![\"\"](\"https:\/\/i0.wp.com\/saipandiabetesblog.com\/wp-content\/uploads\/2017\/02\/diabetic-retinopathy-medicaiton-fenofibrate.jpg?resize=285%2C177\")
Potential concerns<\/h3>\n
My Correspondence with one of our local Pharmacists.<\/h3>\n