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Subspecialties Glaucoma, Basic & Translational Research, Neuro-ophthalmology

Two Diseases, One Stone

Type 2 diabetes increases the risk of glaucoma and, with the latter being the leading cause of irreversible blindness worldwide, there is a need for novel treatments for both conditions. Researchers from the University of Pennsylvania, USA, have linked the real-world use of an approved diabetes drug class, glucagon-like peptide-1 receptor (GLP-1R) agonists, to a reduced risk of being diagnosed with glaucoma (1). The publication is authored by Qi Cui, who was kind enough to answer some of our questions about the work.

What led to you looking at real-world data for his drug class for glaucoma use?

In a previous study, we found that a new, long-lasting GLP-1R agonist, NLY01, rescues neurons that make up the optic nerve in a model of glaucoma (2). This was exciting to us as it suggests that GLP-1R agonists, a class of diabetic medication also approved for weight loss treatment, may be beneficial for glaucoma patients. The link between diabetes and glaucoma, and the devastating effect it can have on patients is why our team was eager to discover if these drugs protect against glaucoma development in diabetic patients.

What was your main finding?

Using data from a national insurance provider, we showed that treatment with GLP-1R agonists (such as exenatide, liraglutide, albiglutide, dulaglutide, semaglutide, or lixisenatide) reduced the chance that diabetic patients will be diagnosed with glaucoma by almost half (44 percent).

Our findings suggest that GLP-1R agonists do not rely on IOP lowering for neuroprotection.

How can this help patients and clinicians?

Although our understanding of what causes glaucoma is improving, available treatments largely rely on lowering intraocular pressure (IOP) using medicines, lasers, or surgery. But lowering IOP can be insufficient to prevent disease progression, or impractical due to low baseline IOP. Our findings suggest that GLP-1R agonists do not rely on IOP lowering for neuroprotection, and will be a novel addition to the therapeutic arsenal available to ophthalmologists should they prove beneficial for treating glaucoma.

The study is retrospective – but the first to highlight a potential benefit of GLP-1R agonists in glaucoma prevention. It is preliminary and certainly not definitive, but it does suggest that clinicians might consider preferentially using GLP-1R agonists in diabetic patients with existing glaucoma risk.

How do you plan to progress this research?

For our follow-up, we will expand upon this study using a large national sampling of patients extracted from the American Association of Ophthalmology’s IRIS Registry. The IRIS Registry is the world’s largest database of ocular diseases and will allow us to examine whether GLP-1R agonists also prevent glaucoma disease progression and improve visual outcomes.

Many other diseases, including age-related macular degeneration in the eye, and Alzheimer’s and Parkinson’s diseases in the brain, involve reactive myeloid cells.

Can your findings be applied to any other diseases?

Our experimental findings suggest that GLP-1R agonists may protect neurons by curbing inflammatory responses in the central nervous system. This inflammatory response involves a class of cells called myeloid cells that’s normally mobilized to fight infections throughout the body, but can also react in a maladaptive fashion to cause tissue damage. Many other diseases, including age-related macular degeneration in the eye, and Alzheimer’s and Parkinson’s diseases in the brain, involve reactive myeloid cells. Because of this, GLP-1R agonists are also being studied by other investigators as a potential treatment for Alzheimer’s disease and Parkinson’s disease.

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  1. J Sterling et al., “Glucagon-like peptide 1 receptor agonist use is associated with reduced risk for glaucoma,” Br J Ophthalmol, bjophthalmol-2021-319232 (2021). PMID: 1234567.
  2. J Sterling et al., “GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension,” Cell Rep, 33, 108271 (2020). PMID: 33147455.
About the Author
Geoffrey Potjewyd

Associate Editor, The Ophthalmologist

The lion’s share of my PhD was spent in the lab, and though I mostly enjoyed it (mostly), what I particularly liked was the opportunity to learn about the latest breakthroughs in research. Communicating science to a wider audience allows me to scratch that itch without working all week only to find my stem cell culture has given up the ghost on the Friday (I’m not bitter). Fortunately for me, it turns out writing is actually fun – so by working for Texere I get to do it every day, whilst still being an active member of the clinical and research community.

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