More Evidence That Fenofibrate Slows Diabetic Eye Disease

[Eddy Edson]

More Evidence That Fenofibrate Slows Diabetic Eye Disease

Significant decline in progression to vision-threatening status, proliferative retinopathy

www.medpagetoday.com

Use of the cholesterol-lowering drug fenofibrate had a modest but statistically significant association with reduced risk of vision-threatening diabetic retinopathy (VTDR), according to results of a large multicenter cohort study.

For the composite endpoint of VTDR, a fully adjusted model showed that fenofibrate use was associated with an 8% lower risk of progression versus non-use (HR 0.92, 95% CI 0.87-0.98, P=0.01).

Fenofibrate use had a more pronounced impact on the risk of proliferative diabetic retinopathy, with a 24% decrease in progression (PDR; HR 0.76, 95% CI 0.64-0.90) but did not significantly affect the risk of developing diabetic macular edema (DME; HR 0.96, 95% CI 0.90-1.03, P=0.27).

The findings are consistent with evidence that fenofibrate may protect against diabetes-associated breakdown of the blood-retinal barrier, although ophthalmologists rarely use the medication to treat diabetic eye disease, reported Brian L. VanderBeek, MD, of the Scheie Eye Institute in Philadelphia, and coauthors, in JAMA Ophthalmology.

"Our positive association for progression to PDR coincides with results of previous clinical trials and adds new information with regards to the impact on DME," the authors stated.

Oz is one of the few countries where fenofibrates are approved for slowing the progression of mild non-proliferative retinopathy, based on older studies mentioned in this piece. The 24% reduction in progression in this latest study is broadly consistent with those older studies, so the Oz approval gains some further support.

Also consistent with those older studies is the lack of any apparent impact on DME.

(I've recently started taking fenofibrates on the advice of my ophthalmologist, but I have to say I'm not clear on the reasoning.

As far as I'm aware, my issue isn't progression from non-proliferative => proliferative, rather it's the risk of DME. I have a whole bunch of microaneurysms in my left eye as a legacy from previous out-of-control T2D, and sometimes one of them close to the retina starts to leak a bit, threatening DME.

I don't know of any reason why fenofibrates would help with that, but I guess it's a question for the ophtho when I see him again in June.)

 

[trophywench]

Perhaps it's a case of , well it won't hurt, and you never know it might help!

 

[Eddy Edson]

On the other hand, fenofibrate seems useless for COVID:

https://twitter.com/x/status/1560794414129491968

(There was a lot of press about a year ago re claims that fenofibrate has a big clinical impact - which haven;t held up.)

 

[Eddy Edson]

Another big study suggesting fenofibrate benefits for DR, this time from South Korea, presented at EASD conference in Stockholm: https://www.medscape.com/viewarticle/981317

And a new thing: reduction in need for Eylea etc for diabetic macular oedema etc.

STOCKHOLM, Sweden — Adding fenofibrate to a statin was associated with an 11% lower risk of diabetic retinopathy progression in patients with type 2 diabetes, new study data show. The drug combination was also found to reduce the risk of intravitreous injection therapy by 22%, a novel observation.

"This finding is not evident from previous clinical trials, where intravitreous injectables were not widely used," said lead author Nam Hoon Kim, MD.
...

His observational, propensity-matched study took a real-world perspective and aimed to determine whether fenofibrate therapy is beneficial in preventing progression of diabetic retinopathy in patients with type 2 diabetes also treated with statins.

Comments from the session moderator are interesting as colour for why fenofibrate haven't been widely adopted for this and other indications where eg the big FIELD trial showed significnt impacts.

"This was an excellent epidemiological study, showing that fenofibrate rescued the eyes from [the effects of] diabetic retinopathy."

"But I seldom use the combination of fenofibrate plus statins," he continued. "The FIELD study showed some positive results, but I think clinicians don't feel fully convinced of fenofibrate, especially compared to statins. ...

"This study is observational, so the evidence level is not very high and we cannot write guidelines based on this. We need a randomized controlled clinical trial," Nyström stressed. "As a clinician, I know that adding fenofibrate to statins can cause side effects, and for this reason, I'd be cautious."

The incremental risks of fenofibrate + statin vs statins by themselves are small or non-existent in the latest studies I have seen but back in the day some earlier trials suggested increases in myalgia etc, and these concerns seem to have become embedded to a certain extent in practice. Anyway, getting my GP past these concerns and accepting my ophtho's recommendation took a bit of work.

I've had zero problems, and in fact fenofibrate may well be the reason I saw a step-change improvement in my PAD soon after I started on them - steps per day, walking speed, reduced PAD-related muscle cramps, leg fatigue, weakness. The same FIELD study which led to the Australian fenofibrate approval for retinopathy also suggested a 30%+ reduction in PAD-related lower limb amputations, with a suggested non-cholesterol related mechanism which might also explain my PAD improvements.

Again, it's a little surprising to me that fenofibrate for PAD has never become a thing; needs more digging ...