The results of the LENS study show that fenofibrate has shown potential in the treatment of diabetic eye disease.
David Preiss教授
For diabetic eye disease, delaying progression is key
Diabetic retinopathy is a common complication of diabetes and a leading cause of vision loss – once progressed to proliferative retinopathy, it can cause vitreous hemorrhage, retinal detachment, and neovascular glaucoma, leading to visual impairment; Diabetic macular degeneration, characterized by exudates, microaneurysms, and/or hemorrhages, can progress to macular edema, which can be sight-threatening in severe cases. Once the disease has progressed to an advanced stage, treatment is limited, expensive, and effective. Therefore, prevention and slowing the progression of the disease is a top priority.
From June 21 to 24, 2024, the 84th Scientific Meeting (ADA) of the American Diabetes Association was held in Orlando, USA. Experts in the field of endocrinology from all over the world gathered together to discuss the latest clinical and basic research results in endocrinology. A randomized controlled study (LENS trial) of 1,151 subjects brought by Dr. David Preiss, Associate Professor and Honorary Consultant of Metabolic Medicine at the University of Oxford, UK, showed that fenofibrate, a commonly used lipid-lowering drug in clinical practice, significantly reduced the risk of diabetic retinopathy progression by 27% compared with placebo during the 4-year follow-up period!
Fig.1 Main results of the study
Re-exploration of old drugs - fenofibrate shows the potential for the treatment of diabetic eye diseases
Fenofibrate is an oral peroxisome proliferation-activating receptor-α (PPARα) agonist that reduces circulating triglyceride and non-high-density lipoprotein (HDL) cholesterol levels. The results of the FIELD (Fenofibrate Intervention and Reduction of Diabetic Events) study in patients with type 2 diabetes showed that there was a reduction in events in the fenofibrate group with retinal laser for proliferative retinopathy or macular edema within 5 years. Retinal imaging subgroup studies in the FIELD and ACCORD trials similarly support the hypothesis that fenofibrate treatment can reduce the progression of diabetic retinopathy. In view of the fact that the above results are derived from non-primary results of the cardiovascular trial, the team led by Professor David Preiss specially designed this study to explore the therapeutic effect of fenofibrate in diabetic eye disease.
Study design
The LENS study was a national (Scotland), randomized, double-blind, placebo-controlled clinical study of 1151 adult participants with type 1/type 2 diabetes mellitus and early mild diabetic retinopathy or macular degeneration (R1, R2, M1, see Table 1). Randomized to receive fenofibrate 145 mg orally daily (n=576; alternate days for patients with impaired renal function) or placebo.
The primary endpoint was a composite endpoint consisting of time to significant disease progression (R3, R4, M2, see Table 1) or time to first treatment (intravitreal injection, retinal laser, vitrectomy). The study was terminated at the ≥ of 222 primary endpoint events or at 4 years ≥.
Figure 2 Study design
Table 1 Grading criteria (diabetic retinopathy and macular degeneration)
At baseline, the mean age of participants was 61 years, 73% were male, 26% had type 1 diabetes, had a mean duration of 18 years, and had a mean HbA1c of 8.2%. The vast majority (96%) have bilateral mild background diabetic retinopathy, and 10% have observable macular degeneration in at least one eye.
Table 2 Baseline characteristics of subjects
27% reduction in the risk of diabetic eye disease progression!
At 4-year follow-up, the combined risk of diabetic eye disease was significantly reduced by 27% in the fenofibrate group. Specifically, 22.7% of participants in the fenofibrate group experienced significant progression/treatment of ophthalmopathy compared with 29.2% in the placebo group (HR = 0.73; 95% CI 0.58-0.91). Among them, the overall risk of retinopathy or macular degeneration progression was reduced by 28% (HR 0.72; 95% CI 0.57~0.91).
Figure 3 Primary and secondary findings
Subgroup analyses showed that fenofibrate treatment was equally effective in patients with type 1 and type 2 diabetes and in patients with normal and/or partially impaired renal function. The incidence of serious adverse events was similar between the fenofibrate and control groups.
Fig.6 Results of subgroup analysis
This article is summarized
In summary, diabetic retinopathy is a common complication of diabetes mellitus and the main cause of vision loss, and delaying disease progression is the top priority of disease management. Results from the LENS study showed that fenofibrate significantly reduced the risk of disease progression over 4 years compared with placebo in people with diabetes and early-stage diabetic eye disease. Treatment with fenofibrate is equally effective in patients with type 1 and type 2 diabetes mellitus and in patients with normal and/or partially impaired renal function.
Resources
[1] Preiss D, et al. NEJM Evid. 2024; doi:10.1056/EVIDoa2400179.
[2] Preiss D.– Results from the LENS trial. Presented at: American Diabetes Association Scientific Sessions; June 21-24, 2024; Orlando.
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