Do SGLT2 Inhibitors Prevent Preclinical Diabetic Retinopathy? A Prospective Pilot Optical Coherence Tomography Angiography Study

Purpose: To evaluate the effects of metformin alone and combined treatment with metformin and an SGLT2 inhibitor on retinal microvascular morphology using optical coherence tomography angiography (OCTA) in isolated type 2 diabetes mellitus (DM) patients with HbA1c above the expected target (>7%).

Methods: Fifty patients with isolated DM, 7%<HbA1c<8%, without diabetic retinopathy (DR) using 500mg metformin ×2 for glycemic control were included in the study. OCTA and BMI measurements were obtained at the first evaluation. Treatment was changed to metformin 1000mg ×2. Patients who did not develop side effects due to the metformin were defined as the metformin-tolerant group (group-1). Patients who developed side effects were defined as the metformin-intolerant group (group-2), and their treatment was changed to metformin 500mg ×2 and empagliflozin 10mg. The second evaluation was performed three months after the last treatment change.

Results: HbA1c was lower on the second evaluation in both groups (P<0.001, in both). On the second evaluation in group-1, a decrease was found in superficial perifoveal and deep parafoveal macular vascular plexus densities (P: 0.040 and P: 0.020, respectively). No statistically significant difference was observed in group-2.

Conclusion: SGLT2 inhibitors may contribute to preventing the development of preclinical DR. In patients with metformin intolerance, adding SGLT2 inhibitors may be a reasonable choice to protect the retina.