Finerenone may slow down the progression of non‐proliferative diabetic retinopathy (NPDR), the early stage of diabetic retinopathy, suggests a recent study published in the journal Diabetes, Obesity and Metabolism.¹ Finerenone also reduced the need for ocular interventions such as laser treatment, intravitreal injection or vitreoretinal surgery in these patients.

A team of researchers from the US, Europe and Japan carried out a combined retrospective pooled analysis of data of routine eye examinations of 244 type 2 diabetes and CKD patients with non‐proliferative diabetic retinopathy (NPDR) in two identical hypothesis-generating clinical trials, ReFineDR and DeFineDR. This data was obtained from the participants in the FIDELIO-DKD and FIGARO-DKD trials. Their aim was to investigate the effect of finerenone on diabetic retinopathy. Out of the 244 patients, 134 had received at least one dose of finerenone and 110 had received placebo.

The primary outcome of this analysis was progression of NPDR manifesting as vision-threatening complication/s comprising of diabetic macular edema, anterior segment neovascularization or progression to proliferative diabetic retinopathy (PDR) in at least one eye up to 2 years after start of therapy (day of randomization in FIDELIO-DKD/FIGARO-DKD). A post hoc analysis was also conducted for time to vision-threatening complication after 2 years and also for time to the required ocular intervention.

At the commencement of the study, 92 (68.7%) of the 134 finerenone-treated patients had mild/moderate NPDR at baseline. Among the placebo recipients, this number was 79 out of 110 (71.8%). Four patients (3.0%) treated with finerenone and 11 (10.0%) of placebo-treated patients had severe NPDR. Baseline HbA1c was comparable between finerenone and placebo groups; 8.25% vs 8.18%, respectively.

After two years of treatment, 5 (3.7%) of the 134 finerenone-treated patients had developed one vision-threatening complication in at least one eye compared to 7 of the 110 participants in the placebo group. In post-hoc analysis, the number was found to increase after 2 years, “with Kaplan-Meier-estimated cumulative incidence probabilities favoring finerenone increasing at 30 months (difference, –0.109) and 36 months (difference, -0.118)”. The researchers further noted that “the numerical benefits of finerenone were consistent for time to DME or progression to PDR and in the subgroup of patients with baseline HbA1c ≤58 mmol/mol and >58 mmol/mol (7.5%)”.¹ Three patients in the finerenone group needed an ocular intervention to manage the vision-threatening complication. On the other hand, nearly 16% patients in the placebo underwent ocular intervention.

Finerenone, a selective, oral nonsteroidal mineralocorticoid receptor antagonist (MRA), was FDA-approved in 2021 to reduce the risk of kidney function decline, kidney failure, cardiovascular death, non-fatal heart attacks and hospitalization for heart failure in adults with diabetic kidney disease associated with type 2 diabetes. The beneficial effects of finerenone, in delaying progression of diabetic nephropathy and reducing risk of cardiovascular outcomes has been demonstrated in two pivotal randomized phase 3 trials - FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) and FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease (FIGARO-DKD).

In the present study, Rossing et al have for the first time analysed the impact of non-steroidal MRA, finerenone, in restricting the advancement of NPDR to DR. By demonstrating the potential benefit of finerenone in delaying the progression of non-proliferative diabetic retinopathy (NPDR) as well as in the prevention of required ocular interventions, this study offers a noninvasive therapeutic alternative to the management of NPDR, which currently involves glycemic control along with control of hypertension, dyslipidemia and other risk factors such as anemia followed by laser photocoagulation is used when the retinopathy is progressing. The number of patients who developed a vision-threatening complication was less with finerenone. Additionally, fewer patients on finerenone required an ocular intervention. Since their trial was exploratory and hypothesis generating and because the options for treatment of DR are limited, the authors suggest randomized trials to verify the potential benefits of finerenone in delaying NPDR progression.

Reference

1. Rossing P, et al. Effect of finerenone on occurrence of vision-threatening complications in patients with non-proliferative diabetic retinopathy: pooled analysis of two studies using routine ophthalmological examinations from clinical trial participants (ReFineDR/DeFineDR). Diabetes Obes Metab. 2022 Nov 4. doi: 10.1111/dom.14915.