medwireNews: Short-term treatment with the sodium-glucose cotransporter (SGLT)2 inhibitor empagliflozin significantly slows the progression of diabetic retinopathy in individuals with type 2 diabetes and a history of nonproliferative diabetic retinopathy (NPDR) compared with dipeptidyl-peptidase (DPP)4 inhibitor treatment, research indicates.
But empagliflozin had no significant impact on the incidence of NPDR in people with type 2 diabetes and no DR history, report the researchers in JAMA Ophthalmology.
“Our study may be helpful when weighing the potential risks and benefits of various glucose-lowering therapies in patients with [type 2 diabetes] who are at high risk of developing DR or among those with preexisting DR,” write Elisabetta Patorno, from Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts, USA, and colleagues.
The team used health insurance claims data collated in the US EMPRISE study to identify patients with type 2 diabetes who began treatment with either empagliflozin or a DPP4 inhibitor (alogliptin, linagliptin, saxagliptin, or sitagliptin) between 2014 and 2019. The researchers used propensity score matching to create 34,239 pairs of individuals who were prescribed empagliflozin or a DPP4 inhibitor and received a new incident diagnosis of NDPR after a vision or retinal examination.
The team also created matched 7381 pairs of adults taking empagliflozin or a DPP4 inhibitor who had a prior history of NPDR and were assessed for progressive disease. Across the incident and progression groups, patients had a similar age (66–67 years), 52% were men, and the average follow-up period was around 8 months.
The risk for incident NPDR did not differ significantly between the empagliflozin and DDP4 inhibitor treatment groups, report Patorno et al, with 31.14 and 29.84 events per 1000 person–years, respectively, and a hazard ratio of 1.04.
However, the risk for DR progression was reduced a significant 22% among those who initiated treatment with empagliflozin versus a DPP4 inhibitor, with respective incident rates of 31.33 and 40.77 per 1000 person–years.
“There are multiple proposed mechanisms by which SGLT2 [inhibitors] may reduce DR progression. SGLT2 receptors are expressed in retinal pericytes and the inhibition of those receptors in the setting of hyperglycemia decreases damage to the retinal microvasculature preventing pericyte loss and repression of angiogenesis,” suggest Patorno and co-authors.
They speculate that the risk reduction seen in the DR progression group could also relate to better control of diabetes and hypertension, and a greater reduction in glycated hemoglobin with empagliflozin than a DPP4 inhibitor.
The team concludes that since the investigation “primarily focused on empagliflozin,” their findings should be “cautiously extrapolated” to other SGLT2 inhibitors.
In an accompanying editorial, Jonathan Shaw and Alicia Jenkins, both from the Diabetes and Population Health Research Laboratory in Melbourne, Victoria, Australia, note that Patorno and colleagues’ study “raises the real possibility that SGLT2 inhibitors may slow the progression of DR.”
However, they point out: “Not all ophthalmologists are comfortable in prescribing systemic drugs such as fenofibrate and empagliflozin.”
The editorialists suggest that “[a]s the evidence continues to grow for such agents, this will need to change, either by taking on this task directly or by developing communication and partnerships with primary care physicians and other physicians to ensure that appropriate prescribing and monitoring occur.” They add that “oral glucose-lowering and lipid-modulating drugs may provide an affordable option” in resource-limited settings.
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JAMA Ophthalmol 2024; doi:10.1001/jamaophthalmol.2024.5219
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