Sodium-Glucose Cotransporter 2 Inhibition in Diabetic Macular Oedema: Emerging Evidence for Stage-Dependent...

Sodium-glucose cotransporter 2 (SGLT2) inhibitors exert systemic cardiometabolic, renal and vascular effects that may influence retinal health, yet whether their effects on diabetic macular oedema (DMO) are stage-dependent remains unclear. We synthesized real-world, interventional and mechanistic evidence on responsiveness across disease stages and retinal phenotypes.

In this scoping review (PRISMA-ScR; prospectively registered, UMIN000061304), we searched PubMed, the Cochrane Library, ClinicalTrials.gov, WHO-ICTRP and Google Scholar for studies published from January 2014 to April 2026. Two reviewers independently screened and charted records. Heterogeneity precluded meta-analysis, so a qualitative meta-summary with exploratory E-value analyses was performed.

Forty studies were included. Large administrative databases consistently associated SGLT2 inhibitor use with a 16%-35% lower DMO incidence (hazard ratio 0.65-0.84) and hazard ratios of 0.53-0.94 for diabetic retinopathy progression. In established DMO, observational studies reported hazard ratios of 0.39-0.81 for anti-vascular endothelial growth factor (VEGF) injections, corticosteroid therapy and repeat vitrectomy, with the first-vitrectomy estimate non-significant, and attenuation in severe non-proliferative or proliferative retinopathy. The only randomized trial (COMET) did not meet its primary endpoint; its fellow-eye and phenotype-specific subgroup analyses were exploratory and hypothesis-generating. Proposed mechanisms include suppression of microglial activation, oxidative stress and angiopoietin-2/VEGF signalling, although translational evidence remains preclinical.

This predominantly observational evidence suggests that SGLT2 inhibitors may be associated with slower DMO disease kinetics across retinopathy stages, with reduced treatment burden most evident before severe retinopathy. Systemic SGLT2 inhibition may complement, rather than replace, anti-VEGF therapy, which remains the cornerstone of DMO management. These findings support prospective stage- and phenotype-stratified investigation.