The SGLT-2 inhibitor, generally used for cardiometabolic and cardiovascular risk reduction, may provide similar benefits for the ophthalmic disease.
Dapagliflozin, an SGLT-2 inhibitor therapy indicated for management of cardiovascular and cardiometabolic risk in adult patients, may be additionally beneficial for the treatment of diabetic retinopathy through its effect on patient glycemic control.
New research presented at the Association for Research in Vision and Ophthalmology (ARVO) 2021 Virtual Sessions showed mouse models treated with dapagliflozin presented with in vivo benefits that would indicate improvements in glycemic control, anti-inflammatory and anti-angiogenic action for diabetic retinopathy.
The findings, from investigators at the Indiana University Department of Ophthalmology, may provide indication for possible human clinical trials assessing the SGLT-2 inhibitor among those with or at risk of diabetic retinopathy development due to their cardiometabolic status.
Led by Ashay D. Bhatwadekar, PhD, RPh, investigators sought to investigate dapagliflozin’s protective effects on diabetic retinopathy development. As they noted the blood glucose-reducing agent’s effect on the ophthalmic disease is not yet interpreted.
The team treated db/db mouse models with dapagliflozin via their diet for 6 months; body weight and food consumption in the models were monitored weekly. Model blood glucose, HbA1c and electroretinogram (ERG) levels were assessed at 2 and 6 months.
At the trial’s end, Bhatwadekar and colleagues processed retinas for tryspin digestions and real-time qPCR.
Human retinal endothelial cells (HRECs) were treated with dapagliflozin concentrations in parallel to the model assessments. Investigators assessed cell viability via Alamar Blue Assay, and migration response was studied via a scratch wound-healing assay.
Though investigators observed no changes in body weight nor food intake in the models, they did note reduced blood glucose and HbA1C with dapagliflozin treatment. The models additionally exhibited greater amplitude for ERG ‘b’ wave, which decreased following dapagliflozin treatment.
Dapagliflozin additionally downregulated mRNA for pro-inflammatory markers, and decreased acellular capillary numbers in the models. All dose-dependent HRECs were viable save for 100 mcM dapagliflozin. Scratch wound-healing assay results showed a significant reduction in wound closure and migration rate after 4 and 8 hours of 50 and 100 mcM dapagliflozin concentrations.
With the positive in vivo outcomes for parameters of diabetic retinopathy care, Bhatwadekar and colleagues concluded dapagliflozin may provide benefit for patients.
“In conclusion, our studies suggest that dapagliflozin could be beneficial in the treatment of DR due to its effect on glycemic control and potential anti-inflammatory and anti-angiogenic action,” investigators wrote.
The study, “Dapagliflozin treatment protects from diabetic retinopathy,” was presented at ARVO 2021.