ORLANDO — The cholesterol drug fenofibrate reduced progression of early eye disease among diabetes patients, the LENS trial showed.

The fibrate reduced progression of early diabetic retinopathy or maculopathy by a relative 27% over 4 years compared with placebo (22.7% vs 29.2%, P=0.006), reported David Preiss, MBChB, PhD, of the University of Oxford in England, at the American Diabetes Association annual meeting. The findings were simultaneously published in NEJM Evidence.

Fenofibrate also reduced the chance of any progression of retinopathy and the risk of developing macular edema.

“The trial addresses a major cause of visual loss for which there are limited therapeutic options,” the researchers noted.

This cheap, generic drug is likely to be cost saving even if it requires monitoring for creatinine elevation, commented Amanda Adler, MD, PhD, also of the University of Oxford.

“It’s preventing or delaying referable diabetic retinopathy,” she told MedPage Today. “Wouldn’t it be nice to not treat diabetic retinopathy, but prevent it in the first place?”

However, there are some practical hurdles, like the question of who would push an off-patent drug like this through regulatory hurdles, noted Adler, who was not involved in the study.

And importantly, Preiss noted: “The huge majority of people, certainly in the U.K., only go to see an ophthalmologist when they run into problems. So if you really want to shift the dial, we have to make up our minds what to do with people with early disease who aren’t seeing a specialist.”

Collaborations and independent individual-participant data meta-analysis are needed to build up the evidence for both types diabetes, said Alicia Jenkins, MBBS, MD, of the Baker Heart and Diabetes Institute in Melbourne, Australia, who spoke at the session regarding her group’s FAME 1 Eye trial testing fenofibrate for early retinopathy in type 1 diabetes patients. “The fact that we’ve got a lot of trials is going to make it easier in the future,” she said.

Fenofibrate is already approved for any level of retinopathy for type 2 diabetes patients in Australia and a number of other countries, she noted. The experience there has been that ophthalmologists might be doing diabetic eye exams but are “not as comfortable, in general, with systemic therapies, and this is where the endocrinologist and perhaps the primary care physicians can be very helpful. So I think getting consensus statements and guidelines will be helpful.”

The LENS trial was conducted within Scotland’s national Diabetic Eye Screening program, which offers regular retinal imaging of patients (ages 12 years and older) with diabetes. LENS randomized 1,151 adults with nonreferrable diabetic retinopathy or maculopathy to receive either 145-mg fenofibrate tablets or placebo.

An open-label run-in with fenofibrate was done prior to randomization to ensure safety. Since fenofibrate is known to reversibly increase blood creatinine levels, estimated glomerular filtration rate (eGFR) had to be at least 40 ml/min/1.73 m2 at screening.

The primary outcome was a composite of developing a grade of diabetic retinopathy or maculopathy that warranted specialist ophthalmic review or required treatment with laser, intravitreal injection, or vitrectomy in either eye.

The trial allowed any type of diabetes other than gestational cases, and 26% of patients enrolled had type 1 diabetes.

Fenofibrate reduced frequency of any progression of retinopathy or maculopathy (32.1% vs 40.2% with placebo, HR 0.74, 95% CI 0.61-0.90) and development of macular edema (3.8% vs 7.5%, HR 0.50, 95% CI 0.30-0.84), with a trend for less treatment of retinopathy (3.0% vs 4.9%, HR 0.58, 95% CI 0.31-1.06).

Visual function, quality of life, and visual acuity were similar between groups. “This may reflect the generally mild retinopathy and well-preserved vision of trial participants such that the trial was likely underpowered to demonstrate any benefit on these outcomes,” the researchers noted.

Trial-averaged eGFR was 7.9 mL/min/1.73 m2 lower in the fenofibrate group compared with the placebo group. Serious adverse events didn’t differ between groups (36.1% on fenofibrate and 35.5% on placebo).

Subgroup analysis showed no suggestion of differential effect by type 1 versus type 2 diabetes or any other characteristic.

The findings were in line with hypothesis generating evidence from cardiovascular trials of fenofibrate, which in pooled data had suggested 23% reduction in diabetic retinopathy progression, Preiss noted.

The trial didn’t show much reduction in lipid levels, supporting the accumulating evidence that fenofibrate mediates its effect directly within the eye, he argued. Animal and human cell model studies point to an impact on retinal vascular leakage and retinal inflammation as well as the blood-retina barrier.

“It was conventionally thought of as a cardiovascular medication. The more you see, the more it looks like a microvascular medication,” Preiss said. “Compared to glucose lowering, it’s easy.”


LENS was funded by National Institute for Health and Care Research. Fenofibrate and placebo were provided for free by Mylan.

Preiss and co-authors disclosed no relationships with industry.

Primary Source

NEJM Evidence

Source Reference: Preiss D, et al “Effect of Fenofibrate on Progression of Diabetic Retinopathy” NEJM Evidence 2024; DOI: 10.1056/EVIDoa2400179.

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