Statins and/or fibrates for diabetic retinopathy: a systematic review and meta-analysis

Abstract

Evidence from observational studies have found a relationship between serum cholesterol and diabetic retinopathy (DR). Apart of the assumption that cholesterolemic control has benefits for patients with diabetes with or without retinopathy, the effects of lipid-lowering drugs have not been properly mapped and critically assessed so far. The objective of this study was to evaluate the effects of statins and/or fibrates on prevention and progression of DR. We conducted a Systematic review of randomized controlled trials (RCTs) following the Cochrane Handbook for Systematic Reviews of Interventions and reported in accordance to PRISMA Statement. GRADE approach was used to summarize the certainty of the evidence. Eight RCTs that fulfilled our eligibility criteria were included, assessing the effects of fibrates (n = 4), statins (n = 3) and fibrate plus statins (n = 1) for therapy (n = 8) or prevention (n = 4) of DR. Overall, the main concern regarding risk of bias assessment was due to incomplete outcome data because high rate of losses in five RCTs. Furthermore, the risk of reporting bias was rated unclear due the lack of previously published protocol in seven RCTs. Fibrates seemed to be associated with a 45% risk reduction of macular edema incidence (Relative Risk 0.55, 95% confidence interval of 0.38 to 0.81, 1309 participants, 2 RCTs, I 2 = 0%, low certainty of the evidence). The certainty of evidence for other outcomes was also very low or low, and we are uncertain regarding the effects of fibrates for DR. Overall, adverse events seemed to be similar between fibrate and placebo, but again based on the width of the confidence intervals, an important increase of adverse events cannot be rule out. The combination statin/fibrate did not seem to have benefit for visual acuity but is likely that further studies can modify this estimate since the current evidence is limited. Adverse events and quality of life were not measured or reported. Concluding, this study found eight RCTs, with limited methodological quality, that assessed the effects of fibrates and/or statins for DR. Based on these findings, we are uncertain about the effects of statins for DR. Fibrates seemed to reduce the incidence of macular edema (low certainty evidence) without increase adverse events (low to very low certainty evidence). Number of Protocol registration PROSPERO CRD42016029746.

Diminished retinal complex lipid synthesis and impaired fatty acid β-oxidation associated with human diabetic retinopathy

“…These findings have important clinical implications. In a systematic review of randomized controlled clinical trials, the effect of statins on DR was uncertain, but fibrates reduced the incidence of macular edema by 45% ( 28 ). Our results illustrate widespread retinal lipid alterations that span a wide array of lipids representative of metabolic pathways above and beyond the cholesterol synthesis pathway.…”

A medication-wide association study to identify medications associated with incident clinically significant diabetic retinopathy

“…39 Findings on the association between fibrates and DR remain controversial. 6 , 8 , 9 , 40 , 41 Two large clinical trials showed that fenofibrate slowed the progression of DR and reduced the need for laser treatment in type 2 diabetic patients with pre-existing retinopathy, 9 , 40 whereas two real-world observational studies did not find such associations. 6 , 8 The discrepancy between our findings and those of previous studies may be explained by different patient populations, different confounding factors controlled for, and the lack of data on lipid profiles in our study.…”

Effect of anticoagulant/antiplatelet therapy on the development and progression of diabetic retinopathy

“…Another study indicated that hypertriglyceridemia may be a surrogate marker of DME [ 38 ]. The effects of fibrates and statins vary; however, the certainty of relevant evidence appeared low in a systemic review [ 39 ]. In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) and its subsequent studies (ADVANCE-on), lower-extremity ulceration or amputation increased the risk of vision-threatening DR [ 40 ].…”