GLP-1 Receptor Agonists and Ocular Health: Benefits and Risks

Rickvir Sidhu

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are injectable or oral medications primarily used for type 2 diabetes mellitus and, increasingly, for obesity management. They act by enhancing glucose-dependent insulin secretion, suppressing glucagon, and promoting satiety, leading to improved glycaemic control and weight loss (1,2). The use of GLP-1 RAs has increased dramatically in recent years. For example, semaglutide prescriptions in the US rose from 2 million monthly in 2021 to 5 million in 2023, with a notable shift toward use in both diabetic and nondiabetic obese populations (3,4). Their impact on ocular health, however, is more complex, with both protective and adverse associations reported.

Protective Associations

Large observational studies suggest GLP-1 RAs may reduce the risk of chronic ocular disease. In a recent propensity-matched cohort, patients with type 2 diabetes receiving GLP-1 RAs had a significantly lower incidence of primary open-angle glaucoma and ocular hypertension compared with metformin users (HR 0.72, 95% CI 0.59–0.88) (5). Similarly, a multicentre study of older adults found GLP-1 RA exposure was associated with a lower hazard of both nonexudative and exudative age-related macular degeneration (AMD) (HR for nonexudative AMD vs metformin 0.68, 95% CI 0.56–0.84) (6). In patients with pre-existing diabetic retinopathy (DR), GLP-1 RAs have also been linked to reduced progression to sight-threatening complications including vitreous haemorrhage, neovascular glaucoma, and blindness (7).

Mechanistically, experimental data indicate GLP-1 RAs exert anti-inflammatory, neuroprotective, and vascular-stabilising effects within the retina, including reduced oxidative stress, improved ganglion cell survival, and attenuation of pathological angiogenesis (8). These pleiotropic effects may underpin the observed epidemiological associations.

Adverse Associations

Conversely, multiple clinical trials and pharmacovigilance studies have raised concerns regarding early worsening of DR and optic nerve disease. The SUSTAIN-6 trial first reported increased DR complications with semaglutide (9), and subsequent meta-analyses confirmed a higher risk of early DR progression, particularly in those with pre-existing disease or rapid glycaemic improvement (RR 1.31, 95% CI 1.01–1.68) (10,11). A recent global pharmacovigilance study also identified significant disproportionality signals for DR (reporting odds ratio (ROR) 17.28, 95% CI 13.62–21.91) and non-arteritic anterior ischaemic optic neuropathy (NAION; ROR 11.12, 95% CI 8.15–15.16) among GLP-1 RA users (12). Further, emerging evidence suggests an increased incidence of neovascular AMD with GLP-1 RA exposure in some populations (13).

Clinical Implications

The apparent duality may reflect differential effects according to baseline ocular status, agent, and glycaemic trajectory. Early worsening of DR is most likely in patients with advanced retinopathy at baseline or rapid HbA1c decline, whereas long-term outcomes may stabilise or improve (7,10).

Current recommendations emphasise close ophthalmic monitoring for patients initiating GLP-1 RAs, particularly those with preexisting DR or at high risk of ocular complications. The American Diabetes Association advises a comprehensive dilated eye examination at baseline and annually for all patients with diabetes, with more frequent follow-up where retinopathy is present or progressing (14). Specifically, retinopathy status should be assessed when intensifying glucose-lowering therapy, including with GLP-1 RAs, given the risk of early worsening linked to rapid glycaemic improvement (14). In patients with moderate to severe DR, more frequent monitoring and cautious glycaemic titration are recommended (14,15). Large cohort studies further support routine screening for all patients treated with GLP-1 RAs, as they face a modestly higher risk of incident DR but paradoxically a reduced risk of sight-threatening complications (7). Pharmacovigilance data underscore the need for vigilance during the first year of therapy, when optic nerve and retinal adverse events appear most frequent (10-12).

Conclusion

GLP-1 RAs hold promise in reducing the burden of glaucoma and AMD but carry risks of early DR worsening and ischemic optic neuropathy, particularly in susceptible patients. Careful ophthalmic monitoring of high-risk individuals remains prudent while further mechanistic and longitudinal studies clarify these associations.

References

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This Post Has 2 Comments

  1. Sujay Nataraja January 25, 2026 Reply

    This article is particularly useful during my GP placement as I am encountering an increasing number of patients prescribed GLP-1 receptor agonists for both diabetes and weight management. Ocular complications are a relatively under-taught area in medical school, and this review provides a clear, balanced overview of both the potential protective and adverse eye effects of these medications. It has helped me better understand when to be vigilant about eye symptoms, the importance of baseline and follow-up eye examinations, and how to counsel patients—especially those with pre-existing diabetic retinopathy—when initiating or reviewing GLP-1 RA therapy in primary care.

  2. Matthew Litchfield-Williams January 31, 2026 Reply

    This article is timely given the rapid rise in GLP-1 receptor agonist prescribing across both diabetic and non-diabetic populations. As a resident doctor interested in primary care, I am increasingly encountering patients on these agents, often with complex comorbidities, and awareness of their potential ocular benefits and risks is clinically valuable. The review succinctly highlights emerging evidence around diabetic retinopathy progression and optic nerve complications, reinforcing the importance of appropriate ophthalmic monitoring and risk stratification. This information is particularly useful for informing clinical decision-making and counselling patients as GLP-1 RA use continues to expand in routine practice.

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