Skip to main content
Top

01-10-2016 | Retinopathy | Review | Article

Fenofibrate and Diabetic Retinopathy

Journal: Current Diabetes Reports

Authors: Jared E. Knickelbein, Akshar B. Abbott, Emily Y. Chew

Publisher: Springer US

Abstract

Diabetic retinopathy, a common and sight-threatening microvascular complication of diabetes mellitus, is a leading cause of blindness among working-aged adults. Medical therapies including intensive control of hyperglycemia and hypertension have been shown to reduce the incidence and progression of diabetic retinopathy. The association of dyslipidemia and treatment with statins with diabetic retinopathy is inconsistent in epidemiologic studies. However, two recent randomized clinical trials have demonstrated beneficial effects of systemic fenofibrate therapy in reducing the progression of diabetic retinopathy independently of serum lipid levels. These findings suggest that fenofibrate may be an effective strategy for reducing the progression of diabetic retinopathy, thus reducing the large and growing public health burden of treating the sight-threatening complications of diabetic retinopathy.
Literature
1.
Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35:556–64.CrossRefPubMedPubMedCentral
2.
Zhang X, Saaddine JB, Chou CF, et al. Prevalence of diabetic retinopathy in the United States, 2005–2008. JAMA. 2010;304:649–56.CrossRefPubMedPubMedCentral
3.
Klein R, Klein BE, Moss SE, et al. The Wisconsin epidemiologic study of diabetic retinopathy. III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years. Arch Ophthalmol. 1984;102:527–32.CrossRefPubMed
4.
Klein R, Klein BE, Moss SE, et al. The Wisconsin epidemiologic study of diabetic retinopathy. II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol. 1984;102:520–6.CrossRefPubMed
5.
Klein R, Lee KE, Gangnon RE, et al. The 25-year incidence of visual impairment in type 1 diabetes mellitus the wisconsin epidemiologic study of diabetic retinopathy. Ophthalmology. 2010;117:63–70.CrossRefPubMed
6.
Hovind P, Tarnow L, Rossing K, et al. Decreasing incidence of severe diabetic microangiopathy in type 1 diabetes. Diabetes Care. 2003;26:1258–64.CrossRefPubMed
7.
Sloan FA, Belsky D, Ruiz Jr D, et al. Changes in incidence of diabetes mellitus-related eye disease among US elderly persons, 1994–2005. Arch Ophthalmol. 2008;126:1548–53.CrossRefPubMedPubMedCentral
8.
Klein R, Klein BE. Are individuals with diabetes seeing better?: A long-term epidemiological perspective. Diabetes. 2010;59:1853–60.CrossRefPubMedPubMedCentral
9.
Guariguata L, Whiting DR, Hambleton I, et al. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014;103:137–49.CrossRefPubMed
10.
Vision Health Initiative (VHI). Report: projection of diabetic retinopathy and other major eye diseases among people with diabetes mellitus United States, 2005–2050. http://​www.​cdc.​gov/​visionhealth/​publications/​diabetic_​retinopathy.​htm. Accessed 22 May 2016.
11.
Diabetic Retinopathy Clinical Research Network, Wells JA, Glassman AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015;372:1193–203.CrossRef
12.
Diabetic Retinopathy Clinical Research Network, Elman MJ, Aiello LP, et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010;117:1064–77. e1035.CrossRef
13.
Photocoagulation for diabetic macular edema. Early treatment diabetic retinopathy study report number 1. Early treatment diabetic retinopathy study research group. Arch Ophthalmol. 1985;103:1796–1806.
14.
Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology. 2008;115:1447–9. 1449 e1441-1410.CrossRefPubMedCentral
15.
Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. The Diabetic Retinopathy Study Research Group. Ophthalmology. 1981;88:583–600.
16.
Silva PAS, Cavallerano JD, Sun JK, et al. Proliferative diabetic retinopathy. In: Ryan SJ, editor. Retina. Philadelphia: Elsevier; 2013.
17.
Writing Committee for the Diabetic Retinopathy Clinical Research Network, Gross JG, Glassman AR, et al. Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA. 2015;314:2137–46.CrossRef
18.
The effect of intensive diabetes treatment on the progression of diabetic retinopathy in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial. Arch Ophthalmol. 1995;113:36–51.
19.
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837–853.
20.••
Chew EY, Ambrosius WT, Davis MD, et al. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med. 2010;363:233–44. The ACCORD study was large randomized clinical trial that demonstrated the benefits of both intensive glucose control and fenofibrate on slowing the progression of diabetic retinopathy.
21.
Reichard P, Nilsson BY, Rosenqvist U. The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med. 1993;329:304–9.CrossRefPubMed
22.
Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998;317:703–713.
23.
Chew EY, Klein ML, Ferris 3rd FL, et al. Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Early Treatment Diabetic Retinopathy Study (ETDRS) report 22. Arch Ophthalmol. 1996;114:1079–84.CrossRefPubMed
24.
Davis MD, Fisher MR, Gangnon RE, et al. Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: early treatment diabetic retinopathy study report #18. Invest Ophthalmol Vis Sci. 1998;39:233–52.PubMed
25.
Ferris 3rd FL, Chew EY, Hoogwerf BJ. Serum lipids and diabetic retinopathy. Early treatment diabetic retinopathy study research group. Diabetes Care. 1996;19:1291–3.CrossRefPubMed
26.
Zhang J, McGwin Jr G. Association of statin use with the risk of developing diabetic retinopathy. Arch Ophthalmol. 2007;125:1096–9.CrossRefPubMed
27.••
Keech AC, Mitchell P, Summanen PA, et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet. 2007;370:1687–97. The FIELD study was the first randomized clinical trial to show a beneficial effect of fenofibrate on slowing the progression of diabetic retinopathy and reducing the requirement for laser treatment.
28.
Keech A, Simes RJ, Barter P, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366:1849–61.CrossRefPubMed
29.
ACCORD Study Group, Buse JB, Bigger JT, et al. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. Am J Cardiol. 2007;99:21i–33i.
30.•
Chew EY, Davis MD, Danis RP, et al. The effects of medical management on the progression of diabetic retinopathy in persons with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) eye study. Ophthalmology. 2014;121:2443–51. This study provided and in-depth analysis on the beneficial effects of strict glucose and fenofibrate on reducing the progression of diabetic retinopahty in the ACCORD study.
31.•
Action to Control Cardiovascular Risk in Diabetes Follow-On Eye Study G, the Action to Control Cardiovascular Risk in Diabetes Follow-On Study G. Persistent effects of intensive glycemic control on retinopathy in type 2 diabetes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Follow-On Study. Diabetes Care. 2016. The ACCORD Follow-On study demonstrated the persistent beneficial effects of pervious strict glucose control on reducing the progression of diabetic retinopathy, while the beneficial effects of fenofibrate were no longer seen after discontinuing therapy.
32.
Bianchi C, Miccoli R, Del Prato S. Hyperglycemia and vascular metabolic memory: truth or fiction? Curr Diab Rep. 2013;13:403–10.CrossRefPubMed
33.
Fenoglide (Fenofibrate) Highlights of prescribing information. http://​www.​accessdata.​fda.​gov/​drugsatfda_​docs/​label/​2012/​022118s005lbl.​pdf. Accessed 4 June 2016.
34.
Mychaleckyj JC, Craven T, Nayak U, et al. Reversibility of fenofibrate therapy-induced renal function impairment in ACCORD type 2 diabetic participants. Diabetes Care. 2012;35:1008–14.CrossRefPubMedPubMedCentral
35.
Mombelli G, Pazzucconi F, Bondioli A, et al. Paradoxical decrease in high-density lipoprotein cholesterol with fenofibrate: a quite rare phenomenon indeed. Cardiovasc Ther. 2010;28:153–60.CrossRefPubMed
36.
Guo J, Meng F, Ma N, et al. Meta-analysis of safety of the coadministration of statin with fenofibrate in patients with combined hyperlipidemia. Am J Cardiol. 2012;110:1296–301.CrossRefPubMed
37.
Keating GM. Fenofibrate: a review of its lipid-modifying effects in dyslipidemia and its vascular effects in type 2 diabetes mellitus. Am J Cardiovasc Drugs. 2011;11:227–47.CrossRefPubMed
38.
Noonan JE, Jenkins AJ, Ma JX, et al. An update on the molecular actions of fenofibrate and its clinical effects on diabetic retinopathy and other microvascular end points in patients with diabetes. Diabetes. 2013;62:3968–75.CrossRefPubMedPubMedCentral
39.
Omae T, Nagaoka T, Tanano I, et al. Fenofibrate, an anti-dyslipidemia drug, elicits the dilation of isolated porcine retinal arterioles: Role of nitric oxide and AMP-activated protein kinase. Invest Ophthalmol Vis Sci. 2012;53:2880–6.CrossRefPubMed
40.
Roy S, Kim D, Hernandez C, et al. Beneficial effects of fenofibric acid on overexpression of extracellular matrix components, COX-2, and impairment of endothelial permeability associated with diabetic retinopathy. Exp Eye Res. 2015;140:124–9.CrossRefPubMed
41.
Garcia-Ramirez M, Hernandez C, Palomer X, et al. Fenofibrate prevents the disruption of the outer blood retinal barrier through downregulation of NF-kappaB activity. Acta Diabetol. 2016;53:109–18.CrossRefPubMed
42.
Kim J, Ahn JH, Kim JH, et al. Fenofibrate regulates retinal endothelial cell survival through the AMPK signal transduction pathway. Exp Eye Res. 2007;84:886–93.CrossRefPubMed
43.
Ding L, Cheng R, Hu Y, et al. Peroxisome proliferator-activated receptor alpha protects capillary pericytes in the retina. Am J Pathol. 2014;184:2709–20.CrossRefPubMedPubMedCentral
44.
Sharma N, Ooi JL, Ong J, et al. The use of fenofibrate in the management of patients with diabetic retinopathy: an evidence-based review. Aust Fam Physician. 2015;44:367–70.PubMed
45.
Jackevicius CA, Tu JV, Ross JS, et al. Use of fibrates in the United States and Canada. JAMA. 2011;305:1217–24.CrossRefPubMedPubMedCentral
46.
Hutton DW, Newman-Casey PA, Tavag M, et al. Switching to less-expensive blindness drug could save medicare part B $18 billion over a ten-year period. Health Aff. 2014;33:931–9.CrossRef

Be confident that your patient care is up to date

Medicine Matters is being incorporated into Springer Medicine, our new medical education platform. 

Alongside the news coverage and expert commentary you have come to expect from Medicine Matters diabetes, Springer Medicine's complimentary membership also provides access to articles from renowned journals and a broad range of Continuing Medical Education programs. Create your free account »