Researchers at Ajou University Hospital said sodium-glucose cotransporter-2 (SGLT-2) inhibitors may be more effective in preventing retinopathy in type-2 diabetes patients, compared to dipeptidyl peptidase-4 (DDP-4) inhibitors.

Recent real-world studies reported a lower risk of cardiovascular events with SGLT-2 inhibitor compared to other glucose-lowering drugs, and the SGLT-2 inhibitors had a lower risk of cardiovascular events compared to DPP-4 inhibitors.

However, such studies failed to report any data on diabetic retinopathy, which is critical to visual prognosis concerning the quality of life in diabetic patients.

The research team, led by Professors Kim Dae-jung, Lee Ki-hwang, and Chung Yu-ri at Ajou University Hospital, compared the effects of SGLT-2 inhibitors with those of DPP-4 inhibitors on the risk of diabetic retinopathy and its progression in people with type-2 diabetes.

The researchers performed a retrospective cohort study among patients with type-2 diabetes, who started on a SGLT-2 inhibitor or DPP-4 inhibitor, by using the National Health Insurance Service database from 2014 to 2016.

Data from the patient group without diabetic retinopathy showed that the risk of developing retinopathy in the SGLT-2 inhibitor group was 11 percent lower than in the DPP-4 inhibitor group.

The SGLT-2 inhibitor’s effect of lowering diabetic retinopathy was more significant in patients with cardiovascular history, in those who took low-dose of aspirin, in people who had fasting blood glucose below 126 mg/dL, and in those whose systolic blood pressure was below 140 mmHg.

However, SGLT-2 inhibitor and DDP-4 inhibitor showed no significant difference in slowing the progression of diabetic retinopathy.

The SGLT-2 inhibitor group had only a 6 percent lower risk of retinopathy progression compared to the DPP-4 inhibitor group among patients with diabetic retinopathy. The difference meant no statistical significance.

“In conclusion, this real-world cohort study showed that the use of an SGLT-2 inhibitor was associated with a lower risk of diabetic retinopathy occurrence but was not different in the risk of diabetic retinopathy progression compared to a DPP-4 inhibitor,” the research team said. “These effects of SGLT-2 inhibitor against diabetic retinopathy are likely mediated in part by its glucose-lowering activity, as well as other mechanisms associated with lowered blood pressure.”

Randomized controlled studies with longer duration are needed to confirm the benefits of SGLT-2 inhibitor concerning the prevention of diabetic retinopathy, the researchers noted.

Professor Kim stressed that the study was meaningful because there was no real-world, randomized, controlled study on the effects of SGLT-2 inhibitors on diabetic retinopathy.

However, the study alone does not indicate that SGLT-2 inhibitors are more effective in preventing retinopathy than DPP-4 inhibitors, but suggests the possibility of prevention, Kim added.

As the number of patients analyzed was limited and the follow-up period was short, there is a need for an additional research that collects foreign data as well as local data to see more significant results, he said.

The study was publihsed in the Diabetes & Metabolism Journal, under the title, "Effects of sodium-glucose cotransporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors on diabetic retinopathy and its progression: A real-world Korean study."

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