Beyond Glycemic Control: Metformin's Multi-Target Role in Preventing and Treating Major Ocular Pathologies
Abstract
Metformin, a first-line therapy for type 2 diabetes, is increasingly recognized as a pleiotropic agent with potential relevance to ocular disease beyond glycemic control. Accumulating epidemiological evidence suggests that metformin exposure may be associated with reduced risk or slower progression of diabetic retinopathy, primary open-angle glaucoma, and age-related macular degeneration, while emerging data also implicate possible benefits in dry eye disease, uveitis, retinal vascular disorders, inherited retinal degeneration, and cataract. Mechanistically, metformin may modulate multiple disease-relevant pathways, including AMPK-mTOR signaling, autophagy, mitochondrial homeostasis, NRF2-mediated antioxidant defense, NF-κB/PARP-related inflammation, VEGF-driven angiogenesis, TXNIP-associated neurodegeneration, and TGF-β-dependent fibrosis. However, current evidence remains insufficient to support metformin as an established ophthalmic therapy. Most clinical data are observational and susceptible to confounding by diabetes severity, comorbidities, treatment indication, and survival bias; randomized evidence is limited, and the METforMIN trial did not significantly slow geographic atrophy progression. In addition, many preclinical studies use concentrations exceeding clinically achievable systemic exposure, whereas ocular pharmacokinetics, tissue bioavailability, transporter dependence, and dose-toxicity relationships remain poorly defined. Signals of dose-dependent risk,…
Read the paper
Related studies
- Metformin as an adjuvant in breast cancer treatment
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?
- Aberrant HSF1 signaling activation underlies metformin amelioration of myocardial infarction in mice
- Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines
- Protein Interaction Network for Identifying Vascular Response of Metformin (Oral Antidiabetic)
- Preventing Long COVID With Metformin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.