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The potential effects of newer groups of glucose lowering drugs on age-related macular degeneration

Eye (2024)Cite this article

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Age-related macular degeneration (AMD) is a multifactorial disease. The prevalence of AMD is expected to rise to 288 million worldwide by 2040 [1]. The pathophysiology of AMD is complex, and the treatment paradigm is suboptimal. Intravitreal anti-vascular growth factor (anti-VEGF) agents such as ranibizumab, bevacizumab, and aflibercept are the most commonly used therapies for exudative neovascular AMD [2]. Novel anti-complement drugs are now proven to slow the progression of geographic atrophy. Metformin, the most commonly used drug for type 2 diabetes, has been demonstrated in recent studies to reduce the risk and progression of AMD. This suggests that metformin may have effects other than glucose decrease [3]. In an effort to slow the progression of AMD, a new trend toward systemic treatment has emerged. Some medications, including fenofibrate, methotrexate, and levodopa, have been introduced as systemic treatments for AMD. They are primarily evaluated because of the similarities of some aspects of the pathophysiology of AMD with other diseases, such as cardiovascular disease and neurodegenerative diseases [4].

Anti-VEGF agents are the standard of care for both neovascular AMD and diabetic retinopathy (DR), emphasising the shared characteristics of these conditions [2, 5]. Some similarities between DR and AMD include inflammation [6, 7], high levels of VEGF [2, 5], and insulin resistance [8, 9] in the retina. These similarities are even more pronounced in neovascular AMD, in contrast to non-neovascular AMD [10]. Even fluctuations in glucose levels within the normal range are significant for retinal health. Within the normal ranges of HbA1C, people with higher HbA1c levels have thinner retina than those with lower HbA1c levels. This highlights the importance of stricter glucose control, especially in patients who do not meet current clinical criteria for prediabetes or diabetes [11]. So, in theory, keeping glucose levels within the normal range at a much younger age before the development of AMD may help protect the retina from the onset and progression of AMD, partly explaining the reduced AMD progression risk. Future research will be required to validate whether the effects of metformin on AMD are due to its effects on blood sugar or other mechanisms of action.

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Authors and Affiliations

  1. School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Moein Ebrahimi

  2. Network of Immunity in Infection, Malignancy, and Autoimmunity, Universal Scientific Education and Research Network (USERN), Tehran, Iran

    Moein Ebrahimi

  3. NIHR Moorfields Biomedical Research Centre, Moorfields Eye Hospital, London, UK

    Sobha Sivaprasad

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Contributions

Moein Ebrahimi and Sobha Sivaprasad were responsible for conceptualization of the paper, conducting the search, screening potentially eligible studies, updating reference lists, and writing and editing the paper.

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Correspondence to Sobha Sivaprasad.

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Competing interests

SS reported receiving financial support from AbbVie, Apellis, Bayer, Biogen, Boehringer Ingelheim, Novartis, Eyebiotech, Janssen Pharmaceuticals, Nova Nordisk, Optos, Ocular Therapeutix, OcuTerra, Roche. SS is also a member of the Eye editorial board. ME has no conflicts of interest.

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Ebrahimi, M., Sivaprasad, S. The potential effects of newer groups of glucose lowering drugs on age-related macular degeneration. Eye (2024). https://doi.org/10.1038/s41433-024-03066-5

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  • DOI: https://doi.org/10.1038/s41433-024-03066-5

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