An investigation led by Brigham and Women's Hospital finds empagliflozin (sold as Jardiance) may reduce the risk of diabetic retinopathy (DR) progression in patients with a history of nonproliferative diabetic retinopathy (NPDR) but showed no association with preventing new NPDR onset.

DR is one of the most common complications of type 2 diabetes, affecting 26% of patients in the United States in 2021. It is the leading cause of irreversible vision loss among working-age adults. This trend is projected to increase in the coming decades.

Empagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT2i) primarily developed for glucose control, has shown benefits for cardiovascular and renal outcomes in past clinical trials. Its association with DR progression has remained unclear.

In the cohort study, "Empagliflozin and the Risk of Retinopathy in Patients With Type 2 Diabetes," published in JAMA Ophthalmology, the team analysed the impact of empagliflozin on DR progression compared to dipeptidyl peptidase-4 inhibitors (DPP4i).

Insurance claims data from Medicare and two major commercial health plans were analysed from a five-year pre-COVID period. Adults with type 2 diabetes who initiated empagliflozin or DPP4i therapy were divided into two groups: 34,239 matched pairs for evaluating the risk of developing new NPDR and 7,831 matched pairs for examining the progression of DR in those with preexisting NPDR. Cohorts were followed for an average of eight months after initiating either treatment.

For incident NPDR, no significant difference was observed between groups. Empagliflozin users had 741 events compared to 712 in the DPP4i group, corresponding to a non-significant HR of 1.04.

For DR progression, empagliflozin users experienced fewer events (158) than the DPP4i group (201), with an HR of 0.78. Cumulative incidence curves showed a divergence favoring empagliflozin for DR progression early in follow-up.

While empagliflozin did not affect the onset of NPDR, it was associated with a 22% reduction in DR progression risk among individuals with preexisting NPDR. Findings are consistent with prior post hoc analyses from the EMPA-REG OUTCOME trial, which showed a similar 22% risk reduction in DR-related events with empagliflozin compared to placebo.

Compared to DPP4i, the team observed no difference in incident DR with empagliflozin, suggesting it has no preventative effect. Empagliflozin's association with reduced DR progression in those with preexisting NPDR makes it a consideration for those with preexisting DR.

The authors suggest that more research is needed to explore long-term outcomes with more complete patient data, such as duration of diabetes, DR severity at baseline, and conducting direct patient evaluations rather than relying solely on claims data.