Fenofibrate slows progression of diabetic retinopathy

ORLANDO, Fla. — An old generic cholesterol drug Fenofibrate Has been shown to potentially slow progression Diabetic retinopathy New trial data suggests that people with early retinal changes may need less retinal laser and intravitreal injection treatments.

Multicenter collaborative study lens In a four-year trial of more than 1,100 subjects randomly assigned to receive fenofibrate or a placebo, fenofibrate reduced the progression or treatment of diabetic retinopathy or maculopathy by 27% in both type 1 and type 2 diabetes patients. Type 2 diabetes It is also effective in people with normal or impaired renal function.

“We'll be looking to see what effect repurposing old medicines can have in routine care. The key is to ensure people don't need medicines. [retinal laser and intravitreal injection]”These treatments have significant drawbacks. If this drug works, the aim is to use it earlier to reduce the number of patients who need treatment,” said lead author Dr David Price. Medscape Medical News.

Price, an associate professor in the Oxford School of Population Health at the University of Oxford in the UK, presented the LENS results at the American Diabetes Association's Annual Scientific Sessions on June 21. Published at the same time NEJM Evidence.

The efficacy of fenofibrate in treating diabetic retinopathy has been confirmed in two previous cardiovascular outcomes trials. 2007 substudy of 2005 FIELD Survey and, 2010 Analysis Based on data from the ACCORD study, LENS is the first dedicated study to investigate the effect of fenofibrate on diabetic retinopathy outcomes, Preiss noted.

Asked for comment, session moderator Thomas W. Gardner, M.D., professor of Ophthalmology, Physical Sciences and Medicine at the University of Michigan, Ann Arbor, said: Medscape Medical News“I think this is very encouraging. It's completely consistent with previous studies. It suggests that we can slow the progression of retinopathy, if not 100%, then perhaps by about a third, which is a big deal. Every little bit helps. And we can do this with a very safe drug, a very inexpensive drug that can be taken orally.”

“Just by controlling it,” Gardner said. A1c But that's not all… If you have small aneurysms or small amounts of bleeding that you can't treat ophthalmically, it seems to me that it makes a lot of sense to give a systemic therapy like fenofibrate.”

Fenofibrate reduced progression by 27%

The 16-centre trial was embedded in routine clinical care at 11 National Health Service centres in Scotland from September 2018 to July 2021. A total of 1151 participants with mild retinopathy or maculopathy were randomised to receive fenofibrate 145mg daily or every other day for patients with renal impairment, or placebo. Complete data were available for 1149 participants; of these, 27% Type 1 diabetes Twenty-three percent had an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m.².

The primary outcome was time to first occurrence of referral-eligible diabetic retinopathy or maculopathy or a composite of diabetic retinopathy or maculopathy treatment (including intravitreal injections, retinal laser therapy, or vitrectomy) in either eye. During treatment, this outcome occurred in 22.7% of patients in the fenofibrate group versus 29.2% in the placebo group, a significant difference (hazard ratio, 0.73; P = .006).

The incidence of progression of retinopathy or maculopathy was also significantly lower with fenofibrate: 32.1% versus 40.2% with placebo (hazard ratio 0.011-0.025). [HR]The incidence of macular edema was 3.8% in the fenofibrate group and 7.5% in the placebo group, which was also significant (HR, 0.50).

There were no differences between the two groups in visual function, quality of life, or visual acuity, which is not surprising, Price noted, because these people had early retinopathy without visual impairment.

Results were similar for participants with type 1 and type 2 diabetes, and whether they had normal or impaired kidney function.

Safety: No major concerns

There were no differences between groups with regard to major cardiovascular events or non-traumatic lower limb amputations, and there were no urinary effects. albumin:Creatinine Ratio. Total and nonHDL cholesterol Although only slightly lower, triglyceride levels were significantly reduced by 13.7% with fenofibrate.

The eGFR was 7.9 ml/min/1.73 m.² The average was lower in the fenofibrate group throughout the study, and the difference was significant, but Dr. Priece noted that this effect was reversible.

“It is well known that fenofibrate increases blood creatinine levels by about 15% on average. This is fully reversible, so if you stop taking the drug after four weeks, your kidney function will return to normal. In fact, after five years, [the FIELD study] This suggests that it may even have a protective effect on the kidneys,” Price told Medscape.

In fact, he added, “If someone who is unfamiliar with the drug looks at renal function, they might mistakenly infer that it's harming the kidneys, when in fact it's not. This is entirely reversible, but we need to be careful to take that into account when we're looking at the patient's renal function, because otherwise we might infer that it's harming the kidneys, when in fact it's probably not. It might have a nephroprotective effect. It's a little quirk that requires delicate attention in clinical management.”

He added that the team plans to follow up on the eye and kidney function of these study participants over the next 10 years.

Price and Gardner told Medscape that they hope two additional ongoing randomized trials will further support the use of fenofibrate in patients with early diabetic retinopathy. One is a three-year trial. Fame 1 Eye The clinical trial is taking place in Australia, where fenofibrate has been approved since 2013 for slowing the progression of diabetic retinopathy in patients with type 2 diabetes.

the other one is, Protocol AFare evaluating approximately 560 patients with type 1 or type 2 diabetes who have mild to moderate nonproliferative diabetic retinopathy and no center involvement. Diabetic macular edemaThe six-year trial will also evaluate the feasibility of a model in which ophthalmologists prescribe fenofibrate or work with primary care physicians and endocrinologists to prescribe fenofibrate and monitor patients.

Gardner noted that it may take time for the ophthalmology community to embrace systemic treatment of early-stage retinopathy: “There's no company marketing this drug or educating ophthalmologists about it. If you go to ophthalmology meetings, you don't hear anything about this right now. I'm sure some will come up, but… ophthalmic surgeons have an incentive to treat advanced-stage disease. They don't have an incentive to treat patients who have a few microaneurysms.”

But, he said, “If I was seeing a patient right now who had mild retinopathy, and whether or not it was perfectly controlled, I would definitely tell them.”

LENS was primarily funded by the National Institute for Health and Care Excellence (NIHR). The Nuffield Department of Population Health (NDPH) at the University of Oxford covered the costs of storing, packaging and preparing the investigational treatment for post. LENS is coordinated by the Clinical Trials Services Unit and Epidemiology Studies Unit (CTSU) at NDPH at the University of Oxford. The CTSU is funded by the UK Medical Research Council (MRC), the British Heart Foundation and the UK Health Data Research (HDR). During the trial, Preiss was also supported by a University of Oxford BHF Centre of Research Excellence Senior Transition Fellowship, the MRC and the UK HDR.

Gardner reports no relevant financial relationships.

Miriam E. Tucker is a freelance journalist based in the Washington, DC area. She's a regular contributor to Medscape and has also contributed to The Washington Post, NPR's Shots blog, and Diatribe. You can find her on X (formerly Twitter) as @MiriamETucker.