Abstract
Background: Diabetic retinopathy (DR) remains a major cause of sight loss worldwide, despite new therapies and improvements in the metabolic control of people living with diabetes. Therefore, DR creates a physical and psychological burden for people, and an economic burden for society. Preventing the development and progression of DR, or avoiding the occurrence of its sight-threatening complications is essential, and must be pursued to save sight. Fenofibrate may be a useful strategy to achieve this goal, by reversing diabetes’ effects and reducing inflammation in the retina, as well as improving dyslipidaemia and hypertriglyceridaemia.
Objectives: To investigate the benefits and harms of fenofibrate for preventing the development and progression of diabetic retinopathy in people with type 1 (T1D) or type 2 diabetes (T2D), compared with placebo or observation.
Search methods: We searched CENTRAL, MEDLINE, Embase, and three trials registers (February 2022).
Selection criteria: We included randomised controlled trials (RCTs) that included people with T1D or T2D, when these compared fenofibrate with placebo or with observation, and assessed the effect of fenofibrate on the development or progression of DR (or both).
Data collection and analysis: We used standard Cochrane methods for data extraction and analysis. Our primary outcome was progression of DR, a composite outcome of 1) incidence of overt retinopathy for participants who did not have DR at baseline, or 2) advancing two or more steps on the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale for participants who had any DR at baseline (or both), based on the evaluation of stereoscopic or non-stereoscopic fundus photographs, during the follow-up period. Overt retinopathy was defined as the presence of any DR observed on stereoscopic or non-stereoscopic colour fundus photographs. Secondary outcomes included the incidence of overt retinopathy, reduction in visual acuity of participants with a reduction in visual acuity of 10 ETDRS letters or more, proliferative diabetic retinopathy, and diabetic macular oedema; mean vision-related quality of life, and serious adverse events of fenofibrate. We used GRADE to assess the certainty of evidence.
Main results: We included two studies and their eye sub-studies (15,313 participants) in people with T2D. The studies were conducted in the US, Canada, Australia, Finland, and New Zealand; follow-up period was four to five years. One was funded by the government, the other by industry. Compared to placebo or observation, fenofibrate likely results in little to no difference in progression of DR (risk ratio (RR) 0.86; 95% confidence interval (CI) 0.60 to 1.25; 1 study, 1012 participants; moderate-certainty evidence) in a population with and without overt retinopathy at baseline. Those without overt retinopathy at baseline showed little or no progression (RR 1.00, 95% CI 0.68 to 1.47; 1 study, 804 participants); those with overt retinopathy at baseline found that their DR progressed slowly (RR 0.21, 95% CI 0.06 to 0.71; 1 study, 208 people; test for interaction P = 0.02). Compared to placebo or observation, fenofibrate likely resulted in little to no difference in either the incidence of overt retinopathy (RR 0.91; 95% CI 0.76 to 1.09; 2 studies, 1631 participants; moderate-certainty evidence); or the incidence of diabetic macular oedema (RR 0.39; 95% CI 0.12 to 1.24; 1 study, 1012 participants; moderate-certainty evidence). The use of fenofibrate increased severe adverse effects (RR 1.55; 95% CI 1.05 to 2.27; 2 studies, 15,313 participants; high-certainty evidence). The studies did not report on incidence of a reduction in visual acuity of 10 ETDRS letters or more, incidence of proliferative diabetic retinopathy, or mean vision-related quality of life.
Authors' conclusions: Current, moderate-certainty evidence suggests that in a mixed group of people with and without overt retinopathy, who live with T2D, fenofibrate likely results in little to no difference in progression of diabetic retinopathy. However, in people with overt retinopathy who live with T2D, fenofibrate likely reduces the progression. Serious adverse events were rare, but the risk of their occurrence was increased by the use of fenofibrate. There is no evidence on the effect of fenofibrate in people with T1D. More studies, with larger sample sizes, and participants with T1D are needed. They should measure outcomes that are important to people with diabetes, e.g. change in vision, reduction in visual acuity of 10 ETDRS letters or more, developing proliferative diabetic retinopathy; and evaluating the requirement of other treatments, e.g. injections of anti-vascular endothelial growth factor therapies, steroids.
Original language | English |
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Article number | CD013318 |
Journal | Cochrane Database of Systematic Reviews |
Volume | 2023 |
Issue number | 6 |
DOIs | |
Publication status | Published - 13 Jun 2023 |
Bibliographical note
Funding Information:Source of funding: grant from Laboratoires Fournier SA, Dijon, France, and the National Health and Medical Research Council of Australia
Funding Information:
The HSC Research and Development (R&D) Division of the Public Health Agency funds the Cochrane Eyes and Vision editorial base at Queen's University Belfast. Queen's University Belfast, UK Gianni Virgili, Co-ordinating Editor for Cochrane Eyes and Vision’s work is funded by the Centre for Public Health, Queen’s University of Belfast, Northern Ireland.
Funding Information:
We would like to thank the following: Iris Gordon for creating and executing electronic search strategies for this review Dr Emily Chew for input to this review’s protocol and for kindly providing us with additional information required for the assessment of the ACCORD trials Leslie Choi, Evidence Synthesis Development Editor (Cochrane Central Executive Team) for comments on the review Katie Curran, MPH, PhD for comments on the review Chiara M. Eandi, Department of Surgical Sciences, University of Torino, Italy for comments on the review Dr Toshi A Furukawa for his input to this review’s protocol Dr Jennifer Evans for her input to this review’s protocol and review Anupa Shah, Managing Editor for CEV for her assistance throughout the editorial process Victoria Pennick for her assistance in copy editing FAME 1 Eye study team and Sarah Howard for providing information of ongoing trials We thank Hsin-wen Wu for translating Cui 2018 Iris Gordon for creating and executing electronic search strategies for this review Dr Emily Chew for input to this review’s protocol and for kindly providing us with additional information required for the assessment of the ACCORD trials Leslie Choi, Evidence Synthesis Development Editor (Cochrane Central Executive Team) for comments on the review Katie Curran, MPH, PhD for comments on the review Chiara M. Eandi, Department of Surgical Sciences, University of Torino, Italy for comments on the review Dr Toshi A Furukawa for his input to this review’s protocol Dr Jennifer Evans for her input to this review’s protocol and review Anupa Shah, Managing Editor for CEV for her assistance throughout the editorial process Victoria Pennick for her assistance in copy editing FAME 1 Eye study team and Sarah Howard for providing information of ongoing trials We thank Hsin-wen Wu for translating Cui 2018 We thank Chin Han Tan for full-text screening and Yan Luo, Hsin-wen Wu, and Nyurguyana Grigoryeva for extracting data.
Publisher Copyright:
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ASJC Scopus subject areas
- Pharmacology (medical)