Sodium-glucose cotransporter 2 inhibition and injection burden in mild diabetic macular edema: An exploratory post hoc analysis of the COMET trial.

AIMS: To investigate the potential of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as a less invasive treatment option for mild diabetic macular edema (DMO) via post hoc subgroup analysis. Previous findings were derived exclusively from observational studies, and no interventional trials based on protocol-defined criteria had been conducted.

MATERIALS AND

METHODS

Based on the COMET trial data, this post hoc analysis targeted mild DME cases, defined by baseline central retinal thickness (CRT) ≤375 μm and best-corrected visual acuity (BCVA) ≤0.155 (logMAR). Patients were randomized to SGLT2i (luseogliflozin) or sulfonylurea (SU, glimepiride) groups. Mild subgroups were compared with the corresponding non-mild cases. The primary outcome was the 48-week frequency of intravitreal ranibizumab injections (IVRs).

RESULTS

In the CRT ≤375 μm subgroup, IVR frequency was significantly lower with SGLT2i vs SU (mean 0.5 ± 1.0 vs 4.3 ± 0.8; P = 0.005, adjusted ancova. Cohen's d of 2.1). The cumulative mean number of IVRs was significantly lower in the SGLT2i group than in the SU group (P = 0.004, hazard ratio 0.29, 95% confidence interval 0.12-0.67). In the BCVA ≤ 0.155 subgroup, whose mean CRT exceeded 400 μm, no significant difference in IVR frequency was observed between the SGLT2i-treated and SU-treated patients. In addition, no intergroup differences were found in patients outside the mild subgroups.

CONCLUSIONS

In this exploratory analysis, SGLT2 inhibition was associated with fewer intravitreal injections in patients meeting the CRT-based mild criteria. These findings are hypothesis-generating and warrant confirmation in future prospective studies.