ArticlePloS one2018
Metformin suppresses retinal angiogenesis and inflammation in vitro and in vivo.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 5 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
73 citing papers in PubMed, 5 syntheses or guidelines pooled it, 133 citations in OpenAlex.
- Environmental risk factors, protective factors, and biomarkers for amyotrophic lateral sclerosis: an umbrella review.Frontiers in aging neuroscience · 2025Pooled it
- Association between metformin use and the risk of developing open-angle glaucoma among patients with diabetes: a retrospective cohort study and meta-analysis.International ophthalmology · 2024 · on this mapPooled it
- Association Between Oral Metformin Use and the Development of Age-Related Macular Degeneration in Diabetic Patients: A Systematic Review and Meta-Analysis.Investigative ophthalmology & visual science · 2022 · on this mapPooled it
- Medications on hypertension, hyperlipidemia, diabetes, and risk of amyotrophic lateral sclerosis: a systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022 · on this mapPooled it
- Enhancing the Efficacy of Metformin in Neoadjuvant Therapy for Breast Cancer: A Meta-Analysis Based on Randomized Clinical Trials.Cancer control : journal of the Moffitt Cancer CenterPooled it
- Dysfunction of the Neurovascular Unit in Diabetic Retinopathy: Advances from Molecular Mechanisms to Targeted Interventions.Stem cell reviews and reports · 2026Review
- Long-Term Metformin Use and Reduced Risk of Age-Related Macular Degeneration: A Large Database Study.Ophthalmology. Retina · 2026Article
- From Diabetes to Degenerative Diseases: The Multifaceted Action of Metformin.International journal of molecular sciences · 2025Review
- Review
- Exploring the Protective Effects of Traditional Antidiabetic Medications and Novel Antihyperglycemic Agents in Diabetic Rodent Models.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Enhancing immunity during ageing by targeting interactions within the tissue environment.Nature reviews. Drug discovery · 2025Review
- Dose-Dependent Relationship Between Long-Term Metformin Use and the Risk of Diabetic Retinopathy: A Population-Based Cohort Study.Clinical drug investigation · 2025Article
- Metformin inhibits pathological retinal neovascularization but promotes retinal fibrosis in experimental neovascular age-related macular degeneration.Frontiers in pharmacology · 2025Article
- Intravitreal Metformin Protects Against Choroidal Neovascularization and Light-Induced Retinal Degeneration.International journal of molecular sciences · 2024Article
- Therapeutic Effects of Metformin on Central Nervous System Diseases: A Focus on Protection of Neurovascular Unit.Pharmaceutical research · 2024Review
- Revamping anti-cGAS-STING therapy via an injectable thermo-responsive supramolecular hydrogel for pathological retinal angiogenesis.Asian journal of pharmaceutical sciences · 2024Article
- Metformin Treatment of Macrophages Increases Microvessel Growth in Three-Dimensional Hydrogel Coculture.Tissue engineering. Part A · 2024Article
- Metformin Modulates Cell Oxidative Stress to Mitigate Corticosteroid-Induced Suppression of Osteogenesis in a 3D Model.Journal of inflammation research · 2024Article
- Revolutionary drug repositioning: the preventive and therapeutic potential of metformin and other antidiabetic drugs in age-related macular degeneration.Frontiers in pharmacology · 2024Article
- Salidroside ameliorates diabetic retinopathy and Müller cell inflammation via the PI3K/Akt/GSK-3β/NF-𝜅B pathway.Molecular vision · 2024Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The oral anti-diabetic drug metformin has been found to reduce cardiovascular complications independent of glycemic control in diabetic patients. However, its role in diabetic retinal microvascular complications is not clear. This study is to investigate the effects of metformin on retinal vascular endothelium and its possible mechanisms, regarding two major pathogenic features of diabetic retinopathy: angiogenesis and inflammation. In human retinal vascular endothelial cell culture, metformin inhibited various steps of angiogenesis including endothelial cell proliferation, migration, and tube formation in a dose-dependent manner. Its anti-angiogenic activity was confirmed in vivo that metformin significantly reduced spontaneous intraretinal neovascularization in a very-low-density lipoprotein receptor knockout mutant mouse (p<0.05). Several inflammatory molecules upregulated by tumor necrosis factor-α in human retinal vascular endothelial cells were markedly reduced by metformin, including nuclear factor kappa B p65 (NFκB p65), intercellular adhesion molecule-1 (ICAM-1), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8). Further, metformin significantly decreased retinal leukocyte adhesion (p<0.05) in streptozotocin-induced diabetic mice. Activation of AMP-activated protein kinase was found to play a partial role in the suppression of ICAM-1 and MCP-1 by metformin, but not in those of NFκB p65 and IL-8. Our findings support the notion that metformin has considerable anti-angiogenic and anti-inflammatory effects on retinal vasculature. Metformin could be potentially used for the purpose of treating diabetic retinopathy in addition to blood glucose control in diabetic patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.