Abstract
AIMS: Anti-vascular endothelial growth factor (VEGF) therapy is the standard treatment for diabetic macular oedema (DMO); however, unmet needs remain. This study aimed to assess the effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in treating DMO. MATERIALS AND METHODS: This multicentre randomised open-label trial included 60 patients with DMO who were eligible for anti-VEGF therapy. Patients were randomised to receive luseogliflozin or glimepiride. Ranibizumab was administered initially to the target eye, with additional doses per protocol. The number of ranibizumab doses up to week 48, and re-admission rates were evaluated. Fellow eye injections were also assessed. RESULTS: Sixty participants, mostly with diabetic retinopathy and half previously treated with anti-VEGF therapy, were included. SGLT2i and sulfonylurea (SU) groups achieved equivalent glycated haemoglobin, central retinal thickness (CRT), and best-corrected visual acuity improvements. Injection frequency for the target eye was similar between groups (SGLT2i vs. SU: 3.9 ± 0.7 vs. 4.7 ± 0.7 times, p = 0.36). Re-administration rates were decreased significantly after the fourth injection in the SGLT2i group (p = 0.030, hazard ratio: 0.45, 95% confidence interval: 0.22-0.92). Fellow eyes in the SGLT2i group showed significant CRT reduction and fewer injections compared with those in the SU group (1.3 ± 0.6 vs. 3.4 ± 0.8, p = 0.016). CONCLUSIONS: Although the overall number of anti-VEGF injections in the target eye showed no significant difference, some patients responded favourably to SGLT2i and required fewer injections. The reduction in fellow eye injections suggests SGLT2i's efficacy in treating early-stage DMO. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry (UMIN000033961); Japan Registry of Clinical Trials (jRCTs031180210).