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Microvascular Residual Risk Studies

21 February 2022
Fenofibrate in diabetic retinopathy: New meta-analysis
In this combined analysis, prolonged fenofibrate treatment reduced the need for retinal laser treatment by over 20% compared with placebo.
Preiss D, Spata E, Holman RR, et al. Effect of fenofibrate therapy on laser treatment for diabetic retinopathy: a meta-analysis of randomized controlled trials. Diabetes Care 2021;
Objective: To evaluate the effect of prolonged treatment with fenofibrate on the need for laser treatment of diabetic eye disease in major trials in patients with type 2 diabetes.
Study design: Systematic review and meta-analysis of randomized placebo-controlled trials investigating the effects of fenofibrate therapy in at least 1,000 patients with diabetes and with intended follow-up over 1 year.
Study population: In total, the analysis included 19,504 type 2 diabetes patients in 3 trials with an accumulated ~80,000 patient-years of follow-up, and a weighted mean follow-up of 4.0 years.
Study outcomes Primary efficacy endpoint: first laser treatment for diabetic retinopathy or maculopathy
Methods: Trial-specific odds ratios (ORs) for first laser treatment were calculated and combined in fixed-effect meta-analyses using Peto’s one-step statistic. A hypothesis-generating analysis investigated the effect of fenofibrate therapy on the need for laser therapy in the first year and subsequent years.

During follow-up, 892 (4.6%) patients, 391 (4.0%) allocated to fenofibrate and 501 (5.1%) allocated to placebo, received retinal laser treatment. Overall, treatment with fenofibrate was associated with a 23% reduction (p = 0.0001) in the odds of laser treatment, equating to a number needed to treat of 88 over 4 years. The effect was greater with prolonged treatment (Table 1).


Events/patients (%)

OR (95% CI)



Fenofibrate (n=9754)





First year

168 (1.7)

185 (1.9)

0.90 (0.73-1.12)


After first year

223 (2.3)

316 (3.2)

0.70 (0.58-0.83)


Any time

391 (4.0)

501 (5.1)

0.77 (0.67-0.88)


CI confidence interval

Conclusion: In conclusion, in a combined analysis of large cardiovascular trials conducted to date, fenofibrate treatment reduced the need for retinal laser treatment by over 20% compared with placebo. To receive worldwide regulatory approvals, allowing widespread use of this generically available and simple treatment to reduce the risk of progressive diabetic retinopathy and maculopathy, it will be necessary to conduct randomized trials primarily designed to test its effect on diabetic eye outcomes. Such studies are under way in subjects with established diabetic retinopathy.


Diabetic retinopathy is one of the leading causes of preventable vision loss and blindness worldwide. Currently, over 100 million people globally have diabetic retinopathy, and the number affected is projected to escalate to over 160 million by 2045, with countries in the Middle East, North Africa and the Western Pacific disproportionately affected (1). Although most individuals have mild disease, they are at risk of progression to more severe disease and thus experiencing a significant decline in health, productivity and quality of life.

Fenofibrate treatment has demonstrated beneficial effects on diabetic microvascular complications in two large randomized clinical trials, in particular reducing the need for retinal laser treatment (2-4). This combined analysis including more than 19,000 individuals with type 2 diabetes focused on the effects of prolonged fenofibrate treatment, as in routine practice.

Compared with placebo, fenofibrate treatment was associated with 23% relative reduction in the need for laser treatment for diabetic retinopathy at any time, with greater effect after the first year of treatment (30% relative risk reduction). However, the authors highlight the need for further studies to investigate the effect of prolonged fenofibrate treatment on specific outcomes of diabetic eye disease, in particular the risk of progressive diabetic retinopathy and maculopathy. Ongoing studies in patients with type 1 and type 2 diabetes (5-7) will provide important insights into the efficacy of prolonged fenofibrate treatment in reducing residual microvascular disease in type 2 diabetes.

References 1. Teo ZL, Tham Y-C, Yu M, et al. Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis. Ophthalmology 2021;128:1580-91.
2. Keech A, Simes RJ, Barter P, et al; FIELD Study Investigators. 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.
3. Chew EY, Ambrosius WT, Davis MD, et al; ACCORD Study Group; ACCORD Eye Study Group. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med 2010;363:233–44.
4. Keech AC, Mitchell P, Summanen PA, et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a andomized controlled trial. Lancet 2007;370:1687-97.
5. Fenofibrate and Microvascular Events in Type 1 Diabetes Eye (FAME 1 Eye) trial;
6. Lowering Events in Non-proliferative Retinopathy in Scotland (LENS) trial;
7. Randomized Clinical Trial Evaluating Fenofibrate for Prevention of Diabetic Retinopathy Worsening;
Key words fenofibrate; diabetic retinopathy; type 2 diabetes; residual microvascular risk