1. METformin for the MINimization of Geographic Atrophy Progression (METforMIN): A Randomized Trial
- Author
-
Shen, Liangbo Linus, Keenan, Jeremy D, Chahal, Noor, Taha, Abu Tahir, Saroya, Jasmeet, Ma, Chu Jian, Sun, Mengyuan, Yang, Daphne, Psaras, Catherine, Callander, Jacquelyn, Flaxel, Christina, Fawzi, Amani A, Schlesinger, Thomas K, Wong, Robert W, Bryan Leung, Loh-Shan, Eaton, Alexander M, Steinle, Nathan C, Telander, David G, Afshar, Armin R, Neuwelt, Melissa D, Lim, Jennifer I, Yiu, Glenn C, and Stewart, Jay M
- Subjects
Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Neurosciences ,Clinical Trials and Supportive Activities ,Aging ,Macular Degeneration ,Eye Disease and Disorders of Vision ,Clinical Research ,Neurodegenerative ,6.1 Pharmaceuticals ,5.1 Pharmaceuticals ,Eye ,Age-related macular degeneration ,Geographic atrophy ,Metformin ,Randomized controlled trial - Abstract
PurposeMetformin use has been associated with a decreased risk of age-related macular degeneration (AMD) progression in observational studies. We aimed to evaluate the efficacy of oral metformin for slowing geographic atrophy (GA) progression.DesignParallel-group, multicenter, randomized phase II clinical trial.ParticipantsParticipants aged ≥ 55 years without diabetes who had GA from atrophic AMD in ≥ 1 eye.MethodsWe enrolled participants across 12 clinical centers and randomized participants in a 1:1 ratio to receive oral metformin (2000 mg daily) or observation for 18 months. Fundus autofluorescence imaging was obtained at baseline and every 6 months.Main outcome measuresThe primary efficacy endpoint was the annualized enlargement rate of the square root-transformed GA area. Secondary endpoints included best-corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) at each visit.ResultsOf 66 enrolled participants, 34 (57 eyes) were randomized to the observation group and 32 (53 eyes) were randomized to the treatment group. The median follow-up duration was 13.9 and 12.6 months in the observation and metformin groups, respectively. The mean ± standard error annualized enlargement rate of square root transformed GA area was 0.35 ± 0.04 mm/year in the observation group and 0.42 ± 0.04 mm/year in the treatment group (risk difference = 0.07 mm/year, 95% confidence interval = -0.05 to 0.18 mm/year; P = 0.26). The mean ± standard error decline in BCVA was 4.8 ± 1.7 letters/year in the observation group and 3.4 ± 1.1 letters/year in the treatment group (P = 0.56). The mean ± standard error decline in LLVA was 7.3 ± 2.5 letters/year in the observation group and 0.8 ± 2.2 letters/year in the treatment group (P = 0.06). Fourteen participants in the metformin group experienced nonserious adverse events related to metformin, with gastrointestinal side effects as the most common. No serious adverse events were attributed to metformin.ConclusionsThe results of this trial as conducted do not support oral metformin having effects on reducing the progression of GA. Additional placebo-controlled trials are needed to explore the role of metformin for AMD, especially for earlier stages of the disease.Financial disclosuresProprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
- Published
- 2024