Evaluating the Effect of Fenofibrate Towards the Progression of Diabetic Retinopathy: A Systematic Review
DOI:
https://doi.org/10.66266/inajemd.v2i2.70Keywords:
Fenofibrate, diabetic retinopathy, macular edemaAbstract
Background: The rising prevalence of diabetic retinopathy (DR) among diabetic patients necessitates innovative therapeutic strategies. Fenofibrate, primarily known for its lipid-lowering
effects, has gained attention for its potential role in mitigating DR progression. This study aims to evaluate the efficacy of fenofibrate in reducing the progression of diabetic retinopathy.
Method: A comprehensive search was done on three electronic databases, including PubMed, Scopus, and ProQuest up to 3 January 2025. We included all studies that are clinical trials or
observational by design published within the last 15 years. The outcome of interest in this study is the progression or worsening of DR. All eligible studies were assessed using the Cochrane risk
of bias tool 2.0 for randomized clinical trials, and the risk of bias in non-randomized studies - of interventions.
Result: A total of 5 studies encompassing 2 RCT and 3 retrospective cohort studies with a total
of 250.835 patients, consisting of 101.026 (40.3%) males, with an overall mean age of 64.3 ± 9.5 years old. Based on the risk of bias assessment, all five studies fall in the low to moderate risk of
bias. Four studies show that fenofibrate significantly reduces the risk of DR progression, while one study shows no significant reduction. Two studies also indicate the efficacy of fenofibrate in
reducing the development of macular edema.
Conclusion: This study solidifies the efficacy of fenofibrate in reducing the risk of DR progression and the development of macular edema.
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References
1. Global Prevalence of Diabetic Retinopathy
and Projection of Burden through 2045 -
Ophthalmology
2. Kusuhara S, Fukushima Y, Ogura S, Inoue
N, Uemura A. Pathophysiology of Diabetic
Retinopathy: The Old and the New. Diabetes
Metab J. 2018 Oct 22;42(5):364–76.
3. Wang W, Lo ACY. Diabetic Retinopathy:
Pathophysiology and Treatments. Int J Mol Sci.
2018 Jun 20;19(6):1816.
4. Keech AC, Mitchell P, Summanen PA, O’Day J, Davis
TME, Moffitt MS, et al. Effect of fenofibrate on the
need for laser treatment for diabetic retinopathy
(FIELD study): a randomised controlled trial. The
Lancet. 2007 Nov 17;370(9600):1687–97.
5. ACCORD Study Group. Effects of Medical
Therapies on Retinopathy Progression in Type 2
Diabetes. N Engl J Med. 2010 Jul 15;363(3):233–
44.
6. Knickelbein JE, Abbott AB, Chew EY. Fenofibrate
and Diabetic Retinopathy. Curr Diab Rep. 2016
Oct;16(10):90.
7. Ong J, Newman D, Sharma N, Ooi JL. The use of
fenofibrate in the management of patients with
diabetic retinopathy: an evidence-based review
[Internet]. Australian Family Physician. The Royal
Australian College of general Practitioners;
8. PRISMA statement [Internet]. PRISMA statement
9. Page MJ, McKenzie JE, Bossuyt PM, Boutron I,
Hoffmann TC, Mulrow CD, et al. The PRISMA 2020
statement: an updated guideline for reporting
systematic reviews. BMJ. 2021 Mar 29;372:n71.
10. ROBINS-I tool | Cochrane Methods
11. RoB 2: A revised Cochrane risk-of-bias tool for
randomized trials | Cochrane Bias [Internet].
12. Preiss D, Logue J, Sammons E, Zayed M,
Emberson J, Wade R, et al. Effect of Fenofibrate
on Progression of Diabetic Retinopathy. NEJM
Evid. 2024 Jul 23;3(8):EVIDoa2400179.
13. Kim NH, Choi J, Kim YH, Lee H, Kim SG. Addition
of fenofibrate to statins is associated with risk
reduction of diabetic retinopathy progression
in patients with type 2 diabetes and metabolic
syndrome: A propensity-matched cohort study.
Diabetes Metab. 2023 May 1;49(3):101428.
14. Meer E, Bavinger JC, Yu Y, VanderBeek BL.
Association of Fenofibrate Use and the
Risk of Progression to Vision-Threatening
Diabetic Retinopathy. JAMA Ophthalmol. 2022
May;140(5):529–32.
15. Lin YC, Chen YC, Horng JT, Chen JM. Association
of Fenofibrate and Diabetic Retinopathy in
Type 2 Diabetic Patients: A Population-Based
Retrospective Cohort Study in Taiwan. Medicina
(Mex). 2020 Jul 31;56(8):385.
16. Wilk A, Wyczechowska D, Zapata A, Dean
M, Mullinax J, Marrero L, et al. Molecular
Mechanisms of Fenofibrate-Induced Metabolic
Catastrophe and Glioblastoma Cell Death. Mol
Cell Biol. 2015 Jan;35(1):182–98.
17. Idris I. Fenofibrate shown to reduce progression
of diabetic retinopathy. Diabetes Obes Metab
Now. 2024;2(7):e108.
18. Fenofibrate for Diabetic Retinopathy Progression
[Internet]. Pharmacy. [cited 2025 Feb 19].
Available from: https://www.pharmacy.umn.edu/
fenofibrate-diabetic-retinopathy-progression
19. Gallucci GM, Alsuwayt B, Auclair AM, Boyer JL, Assis
DN, Ghonem NS. Fenofibrate Downregulates NF-
κB Signaling to Inhibit Pro-inflammatory Cytokine
Secretion in Human THP-1 Macrophages and
During Primary Biliary Cholangitis. Inflammation.
2022 Dec;45(6):2570–81.
20. Varet J, Vincent L, Mirshahi P, Pille JV, Legrand E,
Opolon P, et al. Fenofibrate inhibits angiogenesis
in vitro and in vivo. Cell Mol Life Sci CMLS. 2003
Apr;60(4):810–9.
21. Gong Y, Shao Z, Fu Z, Edin ML, Sun Y, Liegl
RG, et al. Fenofibrate Inhibits Cytochrome
P450 Epoxygenase 2C Activity to Suppress
Pathological Ocular Angiogenesis. EBioMedicine.
2016 Nov 1;13:201–11.
22. Garcia-Ramírez M, Hernández C, Palomer X,
Vázquez-Carrera M, Simó R. Fenofibrate prevents
the disruption of the outer blood retinal barrier
through downregulation of NF-κB activity. Acta
Diabetol. 2016 Feb;53(1):109–18.
23. Bahr TA, Bakri SJ. Update on the Management of
Diabetic Retinopathy: Anti-VEGF Agents for the
Prevention of Complications and Progression of
Nonproliferative and Proliferative Retinopathy.
Life. 2023 Apr 27;13(5):1098.
24. Ocular Anti-VEGF Therapy for Diabetic
Retinopathy: The Role of VEGF in the Pathogenesis
of Diabetic Retinopathy | Diabetes Care |
American Diabetes Association
25. Zhao Y, Singh RP. The role of anti-vascular
endothelial growth factor (anti-VEGF) in the
management of proliferative diabetic retinopathy.
Drugs Context. 2018 Aug 13;7:212532.
26. Cai S, Bressler NM. Aflibercept, bevacizumab
or ranibizumab for diabetic macular oedema:
recent clinically relevant findings from DRCR.
net Protocol T. Curr Opin Ophthalmol. 2017
Nov;28(6):636–43.
27. Boyer DS, Yoon YH, Belfort R, Bandello F, Maturi RK,
Augustin AJ, et al. Three-year, randomized, shamcontrolled
trial of dexamethasone intravitreal
implant in patients with diabetic macular edema.
Ophthalmology. 2014 Oct;121(10):1904–14.
28. Matossian C, Hovanesian J, Bacharach J,
Paggiarino D, Patel K. Impact of dexamethasone
intraocular suspension 9% on intraocular
pressure after routine cataract surgery: post
hoc analysis. J Cataract Refract Surg. 2020
Jan;47(1):53–64.
29. Somayaji S, Gore S, Srinivasa K, Abhilash.
Impact of prednisolone, dexamethasone, and
fluorometholone eye drops on intraocular
pressure in patients post-cataract surgery: A
randomized controlled study - IJCEO
30. Li JX, Hung YT, Bair H, Hsu SB, Hsu CY, Lin CJ.
Sodium-glucose co-transporter 2 inhibitor
add-on therapy for metformin delays diabetic
retinopathy progression in diabetes patients: a
population-based cohort study. Sci Rep. 2023
Oct 10;13(1):17049.
31. Fan YP, Wu CT, Lin JL, Hsiung CA, Liu HY, Lai JN,
et al. Metformin Treatment Is Associated with
a Decreased Risk of Nonproliferative Diabetic
Retinopathy in Patients with Type 2 Diabetes
Mellitus: A Population-Based Cohort Study. J
Diabetes Res. 2020 Apr 19;2020:9161039.
32. Nadelmann JB, Miller CG, McGeehan B, Yu Y,
VanderBeek BL. SGLT2 inhibitors and diabetic
retinopathy progression. Graefes Arch Clin Exp
Ophthalmol Albrecht Von Graefes Arch Klin Exp
Ophthalmol. 2024 Mar;262(3):753–8.
33. Tesyafe H, Paik J, Roh. Empagliflozin and the Risk
of Retinopathy in Patients With Type 2 Diabetes |
Diabetes | JAMA Ophthalmology | JAMA Network
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