Fenofibrate reduces progression of diabetic eye disease
Click Here to Manage Email Alerts
Key takeaways:
- Adults taking oral fenofibrate had a 27% reduction in diabetic eye disease progression over 4 years.
- Fenofibrate is a lipid-lowering drug repurposed for the LENS trial.
ORLANDO — The generic lipid-lowering drug fenofibrate was associated with a significant reduction in progression of diabetic retinopathy and maculopathy, researchers reported.
Data from the Lowering Events in Non-proliferative Retinopathy in Scotland, the LENS trial, were presented at the American Diabetes Association Scientific Sessions and simultaneously published in NEJM Evidence.
“This is really a repurposing study of an old drug, fenofibrate. ... [Fenofibrate is] thought of as a conventional triglyceride-lowering drug but here used in the context of diabetic eye disease,” David Preiss, MBChB, MRCP, FRCPath, PhD, associate professor and honorary consultant in metabolic medicine at the University of Oxford, U.K., said during a press briefing at the ADA Scientific Sessions.
Diabetic retinopathy is among the top five causes of vision loss worldwide — top two among working-age adults in the U.K. — and the only cause to have worsened during the past 30 years, Preiss said. Apart from lowering glucose levels, treatment options for the disease are few and are relatively invasive: laser, intravitreal injection or vitrectomy.
Cardiovascular outcome trials with people with type 2 diabetes suggested that fenofibrate might reduce risk for worsening diabetic eye disease, Preiss said, but LENS is the first trial designed specifically to assess the relationship.
“We needed dedicated trials because all these cardiovascular trials failed to show cardiovascular benefit, so this could have been chance findings from those previous studies,” Preiss said.
For this randomized, double-blind, placebo-controlled trial, Preiss and colleagues randomly assigned 1,151 adults with type 1 or type 2 diabetes and early to moderate diabetic retinopathy or maculopathy to 145 mg fenofibrate orally per day (n = 576; alternating days for participants with impaired kidney function) or placebo. Participants had two in-person visits with researchers and contact by phone every 6 months. The study pills were mailed to participants, who underwent vision screening through Scotland’s national diabetic eye screening program. The primary outcome was referable diabetic eye disease or treatment for diabetic eye disease.
During 4 years of follow-up, participants in the fenofibrate group had a 27% reduction in the primary outcome, according to Preiss.
Among participants in the fenofibrate group, 22.7% progressed to referable or treated eye disease compared with 29.2% of the placebo group (HR = 0.73; 95% CI, 0.58-0.91). Any retinopathy progression occurred in 32.1% of the fenofibrate group vs. 40.2% of the placebo group (HR = 0.74; 95% CI, 0.61-0.9; P = .006), and development of macular edema occurred in 3.8% of the fenofibrate and 7.5% of the placebo groups (HR = 0.5; 95% CI, 0.3-0.84). Of the fenofibrate group, 3% were treated for retinopathy compared with 4.9% of the placebo group (HR = 0.58; 95% CI, 0.31-1.06). Serious adverse events rates were similar between the groups.
“The reduction we saw in cholesterol in our trial was very small. It’s there, it’s significant, but it’s very small,” Preiss said. “To me, unexpectedly, it seems highly likely that this is actually acting in the eye even though you’re taking it as a tablet. And if I can briefly just take a leap of faith, to me this suggests we should test this drug in other conditions, such as macular degeneration. There are common features to macular generation — nothing to do with diabetes and diabetic retinopathy — and it seems to me the next trial has to be tested with macular degeneration as well.”
Reference:
- Preiss D, et al. NEJM Evid. 2024;doi:10.1056/EVIDoa2400179.
Collapse
Preiss D. The effect of fenofibrate on progression of diabetic retinopathy – Results from the LENS trial. Presented at: American Diabetes Association Scientific Sessions; June 21-24, 2024; Orlando.
Read more about
Click Here to Manage Email Alerts