Within the subgroup of people with a history of NPDR at baseline, the risk of progression of DR was 22% lower among those who were treated with empagliflozin. Photo: Jay M. Haynie, OD. Click image to enlarge.

Initially developed for glucose control in patients with type 2 diabetes, empagliflozin and other sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated significant protective effects against adverse cardiorenal outcomes in premarketing and postmarketing randomized clinical trials. Guidelines for the management of diabetes, heart failure and kidney disease all now prominently feature SGLT2 inhibitors. It has been proposed that SGLT2 inhibitors might lower the risk of DR by inhibiting retinal sodium-glucose cotransporter 2 protein. Despite the substantial prevalence of DR and vision-threatening DR in patients with type 2 diabetes, evidence on the role of empagliflozin in DR remains unclear.

Researchers primarily based in the Brigham and Women’s Hospital and Harvard Medical School in Boston investigated the association between empagliflozin use and the risk of incident nonproliferative diabetic retinopathy (NPDR) and DR progression within the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) study, a comparative cohort study based on claims data that aims to monitor the effectiveness and safety of empagliflozin vs. other antidiabetic therapies in patients with type 2 diabetes. This team determined that, compared with initiation of a dipeptidyl peptidase 4 (DPP4) inhibitor, empagliflozin initiation was not associated with incident NPDR, although it may be associated with a lower risk of DR progression.

“Our study may be helpful when weighing the potential risks and benefits of various glucose-lowering therapies in patients with type 2 diabetes who are at high risk of developing DR or among those with preexisting DR,” the study authors wrote in their paper, which was published in JAMA Ophthalmology.¹

A new-user active-comparator cohort study was conducted using US nationwide insurance claims data from two commercial insurers and Medicare over five years. Adults with type 2 diabetes initiating study drugs without prior diagnosis or treatment for proliferative DR or other advanced retinal diseases were included. To assess incident NPDR, patients with a history of NPDR were additionally excluded. A total of 34,239 pairs of propensity-score matched adults were identified in the incident NPDR cohort and 7,831 pairs in the DR progression cohort. In the incident NPDR cohort, 35,867 patients (52.4%) were male, and the mean age was 65.6 years. In the DR progression cohort, 8,229 patients (52.5%) were male, and the mean age was 67.0 years.

Over a mean follow-up period of eight months receiving treatment, the risk of incident NPDR was not different across groups (hazard ratio; HR: 1.04), while the risk of DR progression was lower among individuals who initiated empagliflozin compared with those who began DPP4 inhibitor therapy (HR: 0.78). Results were consistent across multiple subgroups and sensitivity analyses.

“We found that the risk of incident NPDR was not different between groups, and the risk of DR progression in patients with a history of NPDR was 22% lower among those initiating empagliflozin,” the researchers noted.

They suggested that empagliflozin might lower the risk of diabetic retinopathy (DR) by preventing retinal pericyte loss.¹

A commentary also published in JAMA Ophthalmology noted that this finding could help convince eyecare practitioners who are less comfortable prescribing systemic drugs such as fenofibrate and empagliflozin.

“As the evidence continues to grow for such agents, this will need to change, either by taking on this task directly or by developing communication and partnerships with primary care physicians and other physicians to ensure that appropriate prescribing and monitoring occur,” the commentary authors noted. “Furthermore, in resource-limited settings, in which retinal laser equipment and intravitreal drugs and related skilled ocular clinicians may not be readily accessible or affordable, oral glucose-lowering and lipid-modulating drugs may provide an affordable option to limit DR progression.”²