A recent study examined the impact of empagliflozin, a sodium-glucose cotransporter-2 inhibitor, on the risk of nonproliferative diabetic retinopathy and its progression in patients with type 2 diabetes, compared with dipeptidyl peptidase-4 inhibitors.
After significant protective effects against adverse cardiorenal outcomes were shown in premarketing and postmarketing randomized clinical trials with sodium-glucose cotransporter-2 inhibitors (SGLT2is), it has been proposed that they might also lower diabetic retinopathy (DR) risk by inhibiting retinal SGLT2 protein.
The researchers conducted an active-comparator cohort study, in accordance with the EMPRISE study, “to evaluate the risk of nonproliferative diabetic retinopathy (NPDR) onset and DR progression among patients initiating empagliflozin vs a ipeptidyl peptidase-4 inhibitors (DPP4i),” they described in their JAMA Ophthalmology article. They used insurance claims data from two US nationwide commercial insurers and Medicare from August 2014 to September 2019 to identify patients who initiated empagliflozin or a DPP4i treatment for type 2 diabetes (T2D), without prior diagnosis or treatment for advanced retinal disease.
The incident NPDR cohort contained 34,239 matched pairs without prior DR diagnosis and the DR progression cohort had 7,831 matched pairs with prior NPDR. Patients had a mean age of 65.6 years (incident NPDR) and 67 years (DR progression).
The investigators found there was no significant difference in risk between empagliflozin and DPP4i for NPDR, but there was a reduced risk (22%) of progression to more advanced DR among patients with preexisting NPDR who initiated empagliflozin.
They suggested empagliflozin’s potential protective effect on DR progression may stem from inhibition of SGLT2 receptors in retinal pericytes that reduce microvascular damage, improved glycemic and blood pressure control, or both. They wrote: “We also speculate that the risk reduction in DR progression and not incident NPDR could be related to differential hemoglobin A1c reduction by empagliflozin and DPP4i.”
“Our study may be helpful when weighing the potential risks and benefits of various glucose-lowering therapies in patients with T2D who are at high risk of developing DR or among those with preexisting DR,” they concluded.
A full list of author disclosures can be found in the published research.
