Blood Pressure Status Modulates the Therapeutic Response to Sodium-Glucose Cotransporter 2 Inhibitors in Diabetic Macular Edema: A Post Hoc Subgroup Analysis of the COMET Trial.

AIMS: To evaluate the feasibility of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as a systemic adjunct for patients with diabetic macular edema (DME) and hypertension. MATERIALS AND METHODS: This study encompassed a post hoc analysis of the COMET Trial data, focusing on patients with DME and hypertension, defined by office systolic blood pressure (OSBP) ≥ 140 mmHg or a documented history of hypertension. Participants were randomized to receive either SGLT2i (luseogliflozin) or sulfonylurea (SU, glimepiride). The primary outcome was the treatment burden, quantified by the total number of intravitreal ranibizumab injections (IVRs) over 48 weeks. RESULTS: Within the OSBP ≥ 140 mmHg subgroup, 14 patients received SGLT2i and 15 received SU. The total number of IVRs was 4.1 ± 3.1 in the SGLT2i group and 6.8 ± 3.1 in the SU group (Cohen's d = 0.87; power = 0.82). The adjusted analysis of covariance further confirmed significantly fewer IVRs in the SGLT2i group (3.3 ± 1.1 vs. 6.2 ± 1.0, p = 0.025). OSBP was significantly reduced in the SGLT2i group at Week 12, but there was no significant difference at Week 48. Office diastolic blood pressure remained consistently lower in the SGLT2i group. No significant differences in IVR frequency were observed in other subgroups. CONCLUSIONS: SGLT2i may help reduce the treatment burden of IVRs in patients with DME and elevated OSBP. The improvements in blood pressure and visual acuity, despite fewer injections, indicate a potential synergistic effect of SGLT2i in managing DME with hypertension. Further investigation is warranted to validate its efficacy as a potential systemic adjunct. TRIAL REGISTRATION: UMIN000057674.