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      Metformin, A Potential Role in Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

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          Currently, no generally approved medical treatment can delay the onset of age-related macular degeneration (AMD) or slow the progression of degenerative changes. Repurposing drugs with beneficial effects on AMD pathophysiology offers a route to new treatments which is faster, cost-effective, and safer for patients. Recent studies indicate a potential role for metformin in delaying AMD development and progression. In this context, we conducted a systematic review and meta-analysis to look for beneficial associations between metformin and AMD.


          We systematically searched Medline and Embase (via Ovid), Web of Science, and ClinicalTrials.gov databases for clinical studies in humans that examined the associations between metformin treatment and AMD published from inception to February 2021. We calculated pooled odds ratio (OR) with 95% confidence interval (CI) considering a random effect model in the meta-analysis.


          Five retrospective studies met the inclusion criteria. There are no prospective studies that have reported the effect of metformin in AMD. The meta-analysis showed that people taking metformin were less likely to have AMD although statistical significance was not met (pooled adjusted OR = 0.80, 95% CI 0.54–1.05, I 2 = 98.8%). Subgroup analysis of the association between metformin and early and late AMD could not be performed since the data was not available from the included studies.


          Analysis of retrospective data suggests a signal that metformin may be associated with decreased risk of any AMD. It should be interpreted with caution because of the failure to meet statistical significance, the small number of studies, and the limitation of routine record data. However prospective studies are warranted in generalizable populations without diabetes, of varied ethnicities, and AMD stages. Clinical trials are needed to determine if metformin has efficacy in treating early and late-stage AMD.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s40123-021-00344-3.

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          Most cited references 60

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              The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.

              Much of biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalizability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Eighteen items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the web sites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.

                Author and article information

                Ophthalmol Ther
                Ophthalmol Ther
                Ophthalmology and Therapy
                Springer Healthcare (Cheshire )
                12 April 2021
                12 April 2021
                June 2021
                : 10
                : 2
                : 245-260
                [1 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, Department of Eye and Vision Science, , Institute of Life Course and Medical Sciences, University of Liverpool, ; Liverpool, L7 8TX UK
                [2 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, St. Paul’s Eye Unit, , Liverpool University Hospitals NHS Foundation Trust, Member of Liverpool Health Partners, ; Liverpool, UK
                [3 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, Department of Health Data Science, , Institute of Population Health, University of Liverpool, ; Liverpool, UK
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                Funded by: Indonesia Endowment Fund for Education (LPDP), The Ministry of Finance of Republic of Indonesia
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