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Diabetic retinopathy (DR) remains a leading cause of blindness among individuals with diabetes mellitus (DM), with a continuously rising global prevalence. While anti-vascular endothelial growth factor (anti-VEGF) therapy, corticosteroids, laser photocoagulation, and vitreoretinal surgery have improved outcomes, none can permanently prevent disease progression. The complex pathophysiology of DR, which includes inflammation, oxidative stress, and neurodegeneration, highlights the need for additional systemic strategies. This narrative review was informed by a structured search of PubMed, Scopus, and Web of Science covering the period from January 2000 to September 10, 2025. Original studies, systematic reviews, and meta-analyses were included, whereas case reports and editorials were excluded. Findings were synthesized qualitatively. Preclinical models suggest that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert neuroprotective, anti-inflammatory, and antioxidant effects on the retina, preserve the blood-retinal barrier, and reduce vascular endothelial growth factor (VEGF) expression. However, whether these retinal effects are only partially independent of glycemic control remains speculative, as clinical studies have not adequately controlled for changes in glycated hemoglobin (HbA1c) or for differences in concomitant glucose-lowering therapies. Observational clinical studies have associated SGLT2 inhibitor use with a lower risk of DR progression, a reduced incidence of proliferative DR, and fewer vision-threatening interventions compared with some other antihyperglycemic agents. Owing to the established indications in heart failure and chronic kidney disease associated with SGLT2 inhibitors, these agents appear promising for DR prevention and risk modification. However, current clinical evidence is based mainly on observational and retrospective studies and remains vulnerable to confounding and selection bias. Prospective randomized studies with ophthalmic endpoints are needed before firm conclusions can be drawn.
Babović et al. (Tue,) studied this question.