METformin FOR the MINimization (METforMIN) of Geographic Atrophy Progression in Patients with Non-exudative Age-Related Macular Degeneration – A Randomized Trial

Abstract

Purpose : Metformin use has been associated with a decreased risk of age-related macular degeneration (AMD) progression in a number of observational studies. We performed a randomized trial to evaluate the efficacy of oral metformin for reducing the enlargement rate of geographic atrophy (GA) compared with observation.

Methods : We enrolled patients aged ≥ 55 years without diabetes who had GA from AMD in at least 1 eye across 12 clinical centers in a parallel-group randomized trial. We randomized patients to observation or 18 months of 2000 mg daily oral metformin (participants were unmasked). We conducted ophthalmic exam and fundus autofluorescence imaging at baseline, every 6 months through month 18 when the treatment was stopped, and then at month 24. The primary efficacy endpoint was the annualized enlargement rate of the square root of total GA area measured on autofluorescence images. We also assessed patients’ best-corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) at each visit.

Results : Of 66 participants enrolled from October 2016 – January 2020, 44 completed the study. 23 patients (37 eyes; BCVA = 59.7 ± 16.6 letters) were in the observation group and 21 patients (34 eyes; BCVA = 61.0 ± 16.1 letters) were in the treatment group. The mean ± standard error annualized enlargement rate of square root of GA area was 0.35 ± 0.05 mm/year in the observation group and 0.41 ± 0.05 mm/year in the treatment group (risk difference = 0.06, 95%CI -0.20-0.08 mm/year; P = 0.38; Figure). The mean ± standard error decline rate in BCVA was 3.7 ± 1.3 letters/year in the observation group and 3.3 ± 1.0 letters/year in the treatment group (P = 0.72). The mean ± standard error LLVA decline rate was 5.8 ± 1.9 letters/year and 1.6 ± 2.0 letters/year for the observation and treatment group, respectively (P = 0.13). No serious adverse events were related to metformin use.

Conclusions : We were unable to demonstrate a significant association between use of metformin and GA progression. Future randomized trials may be needed to assess the impact of metformin on earlier stages of AMD.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Figure. Mean changes in the square root of GA area (mean ± 95% confidence interval). N = 37, 35, 30, 29, and 15 in the observation group and 34, 31, 29, 24, and 18 in the metformin group.