Long-term use of SGLT2 inhibitors may prevent diabetic retinopathy progression in diabetes patients

"The anti-diabetic treatment with an SGLT2 inhibitors add-on was associated with a significantly higher risk of diabetic retinopathy progression in the short term but a remarkably lower risk of DR progression in the long term," the researchers reported.

They added, "The continued SGLT2is add-on therapy may yield benefits beyond glycemic control for patients with diabetic retinopathy."

Diabetic retinopathy is the most common complication in diabetes mellitus and is the leading cause of blindness. Among diabetes patients, the global prevalence of DR is 22.27%. Despite this, the underlying mechanisms of DR are not fully understood due to its complex pathophysiology.

SGLT2 inhibitors, including canagliflozin, dapagliflozin, and empagliflozin are widely used for type 2 diabetes (T2D) treatment. Their use in clinical practice is often for the blood glucose regulation in T2D patients prone to heart failure, due to their associated benefit to cardiovascular (CV) outcomes. However, there have been no reports of a large-scale population study on the effects of SGLT2 inhibitors on diabetic retinopathy and according to the authors, the real-world outcomes have not been validated.

To fill this knowledge gap, Chun-Ju Lin, School of Medicine, China Medical University, Taichung, Taiwan, and colleagues aimed to investigate how SGLT2is add-on therapy for metformin affects diabetic retinopathy progression in patients with type 2 diabetes in a nationwide population-based study conducted from 2016 to 2018.

The study involved 3,432,911 adults with type 2 diabetes in Taiwan. Data on age, sex, income, diabetes complication severity index score, comorbidities, staging of kidney disease, index year, and anti-diabetic medications were included. The outcome was a progression of diabetic retinopathy, determined by procedure codes or the addition of ICD-10-CM or ICD-9-CM codes to the patient's medical records during the study. To validate the findings, sensitivity analyses were performed.

The study led to the following findings:

• The adjusted hazard ratio (aHR) of DR progression was 0.89 for the SGLT2is add-on group, relative to the control group.
• The Kaplan–Meier curve of the cumulative incidence rate showed that the cumulative incidence of DR progression was considerably decreased in the SGLT2is cohort.
• The use of SGLT2is for less than one year and 1–2 years were associated with a significant increase in the risk of DR progression (aHR 1.56 and 1.88, respectively); however, the risk markedly reduced if the SGLT2is regimen was used for more than 2 years (aHR 0.41).
• The serial sensitivity analysis showed consistent findings.
• The aHR of DR progression was 0.82 for the SGLT2is cohort relative to the non-SGLT2is cohort based on the fundoscopy or indirect ophthalmoscopy findings within one year before the outcome date.

"The eyes of patients with an elevated ocular risk should be evaluated before commencing aggressive therapies to achieve glycemic control," the investigators suggested.

"Long-term treatment with an SGTL2 inhibitor without interruption may effectively prevent DR progression," they concluded.

Reference:

Li, J., Hung, Y., Bair, H., Hsu, S., Hsu, C., & Lin, C. (2023). Sodium-glucose co-transporter 2 inhibitor add-on therapy for metformin delays diabetic retinopathy progression in diabetes patients: A population-based cohort study. Scientific Reports, 13(1), 1-12. https://doi.org/10.1038/s41598-023-43893-2