Association of metformin use with age-related macular degeneration risk

Abstract Background: The association between metformin use and reduced age-related macular degeneration (AMD) risk has been explored. Studies have shown a positive association, no association, or ambiguous results. The aim of this narrative review is to compile these divergent findings, and thereby, better assess the potential of metformin use in reducing the AMD risk. Methods: Studies were extracted in two ways. First, a standard Google Scholar™ search was performed using the keywords “metformin” AND “macular degeneration” without language or time restrictions. The full texts of relevant articles identified in this search were retrieved and assessed, and articles of peer-reviewed original studies and meta-analyses were included. Second, the reference lists of the included articles were used to identify additional articles that satisfied the search algorithm and included in this review. Results: Of the ۱۲ studies included in this review, eight showed a positive correlation between metformin use and a reduced AMD risk, while one showed no association. Of the eight positive studies, seven were retrospective. Apart from the design, the studies were also diverse. The number of participants in each study ranged from over ۳۰۰ to ۳۰ million person-years. The study populations included those with type ۲ diabetes mellitus, those with AMD, and those without either. The study locations were the United States, Europe, and Asia. The ambiguous or negative results from four studies could largely be rationalized based on the confounding factor of study design. Conclusions: Most studies examined in this review demonstrated a positive association between metformin use and a reduced AMD risk. Studies not reporting such an association did not definitively demonstrate its absence. Overall, the studies reviewed herein support further clinical investigation of metformin as a prophylactic and potential treatment modality for AMD. Further randomized clinical trials with reasonably longer follow-up periods are necessary to determine the generalizability of the findings of studies reporting positive results. Keywords: metformin hydrochloride type ۲ diabetes mellitus age-related macular degeneration retinal pigment epithelium cell senescence dry AMD exudative AMD wet macular degeneration geographic atrophy macular degeneration