Metformin therapy as a strategy to compensate anti-VEGF resistance in patients with diabetic macular edema

Diabetic macular edema (DME) is the complication of diabetic retinopathy, the leading cause of vision loss among diabetic patients. Metformin is the main antidiabetic treatment. It is preferable for its great anti-angiogenic and anti-inflammatory effects. Anti-vascular endothelial growth factor (VEGF) therapy is the preferable treatment for DME despite its lack of convincing results in some patients. To assess whether the combination of metformin and anti-VEGF drugs may decrease the risk of anti-VEGF resistance among DME patients. We included DME patients with a central retinal thickness (CRT) ≥ 250 μm who consecutively underwent at least 3 anti-VEGF therapies from January 1, 2020, to December 30, 2021. Anti-VEGF resistance was defined as persistent macular edema with decreased CRT ≤ 25% after 3 anti-VEGF injections. 109 patients were considered for this research, of whom 65 (59.6%) were resistant to anti-VEGF therapy. The mean CRT of the non-metformin group decreased from 344.88 ± 129.48 to 318.29 ± 123.23 (20.85%) and from 415.64 ± 144.26 to 277.11 ± 99.25 (31.51%) (P = .031) in the metformin group. Moreover, the metformin group had fewer resistant patients than the non-metformin, 24 (45.3%) versus 41 (73.2%). Furthermore, a considerable gain in visual acuity was observed in both groups, with a BCVA gain of 40.41% in the metformin group and 39.9% in the non-metformin group. Metformin may be combined with an anti-VEGF drug to minimize the risk of anti-VEGF resistance among DME patients. Moreover, it can serve to design effective therapeutic deliveries.