Empagliflozin Associated with Reduced Risk of Diabetic Retinopathy Progression in T2D

New results from the EMPRISE study suggest the initiation of empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, may reduce the risk of diabetic retinopathy progression in adults with type 2 diabetes (T2D).¹

The results, presented at the 83rd Scientific Sessions of the American Diabetes Association (ADA 2023), showed empagliflozin treatment was associated with a 23% reduction in the risk of diabetic retinopathy progression, compared with Dipeptidyl peptidase 4 inhibitors (DPP4i), and a similar risk of nonproliferative diabetic retinopathy (NPDR) onset.

“Our data suggest that the initiation of empagliflozin may be beneficial in patients with diabetic retinopathy,” presenting investigator Helen Tesfaye, PharmD, MSc, from the division of pharmacoepidemiology at Brigham and Women’s Hospital, Harvard Medical School, said at ADA 2023. “These results may be helpful when weighing the potential risks and benefits of various glucose-lowering agents in adults with T2D and diabetic retinopathy.”

Diabetic retinopathy is the leading cause of blindness among working-age adults and by 2050, is projected to affect approximately 16 million people with diabetes in the United States.² Results from large outcome trials have shown the benefit of empagliflozin on both cardiovascular and renal outcomes for patients with T2D. However, the role of the therapy class is not completely understood with respect to diabetic retinopathy.

A post-hoc analysis of the EMPA-REG OUTCOME trial showed that, compared with placebo, empagliflozin reduced the risk of retinopathy by 22%. Meta-analyses of other randomized controlled trials indicated a potential protective effect of SGLT2 inhibitors for DR. Still, investigators noted this was not a pre-specified primary endpoint and was rather looked at as an adverse or safety event.

The EMPRISE trial set out to analyze the effectiveness and safety of empagliflozin in patients with T2D in routine care.¹ The investigative team researched 2 diabetic retinopathy outcomes among adults with T2D initiating empagliflozin or DPP4i in 2 cohorts.

Tesfaye and colleagues measured the risk of NPDR for cohort 1 and the risk of diabetic retinopathy progression for cohort 2 using data from Medicare-fee-for-service and 2 US commercial claims databases (Optum Clinformatics Data Mart and IBM Marketscan) from August 2014 - September 2019. Those who had T2D and initiated empagliflozin or a DPP4i during the study period were included in the analysis.

To evaluate the onset of NPDR, the team identified a total of 34,262 1:1 propensity-score matched patient pairs without a history of any diabetic retinopathy. To evaluate the progression of diabetic retinopathy, the team identified 7,839 1:1 propensity-score matched patient pairs with a history of NPDR and without diagnosis or treatment for advanced diabetic retinopathy prior to cohort entry. They estimated pooled hazard ratios and the rate difference (RD) per 1,000 person-years with 95% confidence intervals (CIs) adjusting for 143 baseline covariates.

Upon analysis, compared to DPP4i, a similar risk of NPDR onset was shown with the initiation of empagliflozin (HR, 1.05 [95% CI, 0.95 - 1.16]; RD, 1.52 [95% CI, -1.61 to 4.65]). Empagliflozin treatment was also associated with a decreased risk of diabetic retinopathy progression (HR, 0.77 [95% CI, 0.62 - 0.95]; RD, -9.49 [95% CI, -16.90 to -2.06), over a mean follow-up of ~8 treatment months.

Investigators noted the results were consistent in both direction and magnitude as the similarly defined retinopathy outcome in the EMPA-REG OUTCOME Trial (HR, 0.78; 95% CI, 0.54 - 1.12).

References

1. Tesfaye H, Htoo PT, Paik JM, Zakoul H, Schmedt N, Deruaz-Luyet A, Koeneman L, Wexler DJ, Patorno E. Empagliflozin on the Risk of Retinopathy in Patients with Type 2 Diabetes—Results from the EMPRISE Study. Oral presentation at the 83rd Scientific Sessions of the American Diabetes Association. June 23 – 26, 2023.
2. Saaddine JB, Honeycutt AA, Narayan KMV, Zhang X, Klein R, Boyle JP. Projection of Diabetic Retinopathy and Other Major Eye Diseases Among People With Diabetes Mellitus: United States, 2005-2050. Arch Ophthalmol. 2008;126(12):1740–1747. doi:10.1001/archopht.126.12.1740