GLP-1 Clinical Trial Eye Safety: Understanding Semaglutide Eye Side Effects

GLP-1 receptor agonists, such as semaglutide, have emerged as powerful therapeutic agents, transforming the management of type 2 diabetes, weight management, and cardiovascular health.

With transformative weight loss results, reduced cardiovascular risk, and improved glycemic control reported by millions of patients, they’ve quickly risen to fame as “miracle drugs” with people running to their doctor for a prescription. 

It’s estimated that 6% of the adult U.S. population, roughly 15 million people, were prescribed GLP-1 weight loss drugs in 2024, including FDA-approved brand names like Ozempic, Wegovy, and Rybelsus. 

As social media celebrates dramatic results from semaglutide use for obesity and blood sugar control, growing evidence suggests these drugs may carry a higher risk of eye health complications, making semaglutide eye side effects an issue that deserves far more attention.

These “miracle drugs” may come with a blinding side effect — literally.

Multiple studies published in the past two years, along with mounting real-world pharmacovigilance data, are all pointing to a similar warning: GLP-1s may significantly increase the risk of serious, sometimes irreversible ocular conditions. These include nonarteritic anterior ischemic optic neuropathy (NAION), neovascular age-related macular degeneration (nAMD), progression of diabetic retinopathy (DR), and other forms of retinal vascular compromise. And the most troubling part? These risks are often unknown or overlooked by the general public.

GLP‑1 Clinical Trial Eye Safety: The Data Is Piling Up 

1. 4x Increased Risk of NAION with Semaglutide

In a landmark 2024 study published in JAMA Ophthalmology, researchers followed diabetic and obese patients exposed to semaglutide. What they found was shocking: the risk of developing NAION, a condition that causes sudden, painless, and often permanent vision loss, was significantly higher in those using the drug. Diabetic patients had a hazard ratio of 4.28, while overweight or obese non-diabetic patients faced an even greater risk with a hazard ratio of 7.64. [1]

The study found that most NAION cases occurred within the first year of treatment, suggesting that the initial rapid metabolic shifts caused by semaglutide may trigger ischemic events in the optic nerve. This places an urgent emphasis on early ophthalmic monitoring, ideally before the first dose.

2. GLP-1s Double the Risk of nAMD in Diabetics

A more significant concern is emerging from population-level data. A 2025 study published in JAMA Ophthalmology tracked over 139,000 patients (mean age 66 years). It revealed that diabetic GLP-1 users had a more than twofold increased risk of developing nAMD, a sight-threatening condition characterized by abnormal blood vessel growth in the retina. The study also showed that the longer the duration of GLP-1 exposure, the greater the risk of nAMD. [2]

3. Global Pharmacovigilance Confirms Potential Risk Patterns

Analysis of two of the world’s largest pharmacovigilance systems — FAERS and VigiBase — has corroborated these findings at an international level. These massive databases aggregate millions of adverse event reports from real-world clinical settings. [3]

• In the U.S. FAERS database, semaglutide was associated with a reporting odds ratio of 17.28 for diabetic retinopathy and 11.12 for NAION.
• The WHO’s VigiBase confirmed these risks with even higher reporting odds ratios, including an ROR of 68.58 for ischemic optic neuropathy.

These are not isolated case reports. They reflect thousands of patients across dozens of countries and a consistent, clinically meaningful incidence of serious eye disease, reinforcing a clear signal of vision-threatening eye conditions associated with semaglutide exposure.

Clinical Implications for Patients and Providers

For patients, this means that taking a GLP-1, even with a clean bill of ocular health, introduces a new category of risk. Vision loss may come without warning, and in some cases, it may be irreversible (see risk factors below).

For providers, this creates a new obligation to treat the eyes as part of systemic care. Patients starting on GLP-1s should undergo a baseline comprehensive eye exam, including fundus photography and, ideally, OCT. They should be monitored every 6 to 12 months, depending on pre-existing conditions.

Unfortunately, most providers do not have an ophthalmic referral process built into their GLP-1 workflow, leaving patients exposed. This creates a dangerous blind spot in our understanding of drug safety.

Risk Factors for Vision Loss in GLP-1 Users

Emerging evidence from the American Optometric Association (AOA) highlights specific risk factors that elevate a patient’s chances of developing GLP-1–associated ocular complications. [4] These include:

• Diabetes mellitus – already a known contributor to diabetic retinopathy and NAION.
• Hypertension – vascular stress may compound ischemic events.
• Hyperlipidemia – associated with atherosclerosis affecting retinal circulation.
• Obstructive sleep apnea – a known comorbidity that increases NAION risk.
• “Disc at risk” anatomy – a small cup-to-disc ratio in the optic nerve is the strongest anatomical risk factor for NAION.
• Optic nerve head drusen – particularly in younger patients, may increase crowding at the nerve head.

The AOA also notes that sudden vision loss, visual field defects, or color vision changes may be early signs of NAION and should prompt immediate evaluation and discontinuation of GLP-1RAs if confirmed.

Clinical Recommendations from the AOA

According to the AOA’s Evidence-Based Optometry Committee (June 2025), doctors managing patients on GLP-1 receptor agonists should implement the following protocols [4]:

• Baseline in-person, comprehensive, dilated ocular fundus examination upon starting a GLP-1RA should be performed.
• Baseline ocular fundus photography and possibly OCT for documentation are beneficial for those most at risk.
• Closer follow-up and examination of patients on GLP-1RAs within the first 12 to 18 months of starting the medication.
• Advise patients starting a GLP-1RA of the potential ophthalmic complications.
• Advise patients if they have risk factors such as associated systemic diseases, a disc at risk, optic nerve head drusen, or worsening DR.
• Advise patients to return to the clinic for evaluation immediately for any change in vision.
• If NAION is confirmed, treatment with GLP-1RA should be discontinued, and the patient’s health care team should be consulted immediately.

By adopting these protocols, eye care professionals and clinical researchers can reduce the risk of vision loss associated with GLP-1 therapies by enabling earlier detection of conditions such as NAION and diabetic retinopathy, supporting safer semaglutide use, and better long-term eye health.

What We Can Do Right Now

At 20/20 Onsite, we bridge the gap between systemic care and vision protection by delivering specialized ophthalmology expertise through our Mobile Vision Clinics (MVCs). Our clinical trial solutions bring protocol-ready eye exams, retinal imaging, and optic nerve monitoring directly to the point of need, supporting early detection of vision changes associated with GLP-1 therapies such as semaglutide and reducing the risk of serious eye disease in clinical trials.

If you’re running or sponsoring a study involving GLP-1s, we offer:

• Turnkey ophthalmic assessments, including visual acuity, fundus photography, OCT, dilated retinal exams, etc.
• Centralized image review and data harmonization to ensure quality and consistency.
• Custom protocol design to integrate vision safety as a primary or secondary outcome.
• Mobile delivery, bringing eye exams directly to research sites or patients’ homes for decentralized trials.

These capabilities enable earlier detection and more comprehensive regulatory documentation, ultimately improving both patient safety and trial outcomes.

Why This Needs to Happen

With one in eight adults (12%) indicating they have ever taken a GLP-1 agonist in the US, GLP-1 use is exploding across populations and age groups. Indications now include cardiovascular risk reduction, polycystic ovary syndrome (PCOS), and even prediabetes.

And yet, the American Diabetes Association estimates that fewer than 50% of people with diabetes undergo annual eye exams. This alarming estimate suggests that many GLP-1 patients are also under-screened. That’s a massive gap in proactive care.

If we don’t act quickly to monitor and mitigate these risks, thousands more patients may suffer avoidable vision loss, often beginning with subtle symptoms like blurred or blurry vision that go unnoticed. Without proactive screening for diabetic eye disease and other vision-threatening conditions, this gap in care could lead to irreversible outcomes, representing a profound failure of modern, evidence-based medicine.

Our Call to Action

• To providers: Refer patients for eye exams as soon as GLP-1 therapy is initiated.
• To patients: Don’t wait until something feels wrong. Get your eyes checked now.
• To sponsors and CROs: Let us help you collect the ophthalmic data that regulators will soon require, ensuring patient safety.

Final Thought: A Miracle Drug Shouldn’t Take Your Sight

GLP-1s are here to stay, and their benefits for blood sugar levels and weight management are real. But no drug is above scrutiny. Growing clinical studies and recent evidence around semaglutide eye side effects underscore the need to protect eye health and address risks like blurred vision and vision loss before they become irreversible.

At 20/20 Onsite, we believe vision protection must be part of responsible GLP-1 use. Whether you’re a researcher, healthcare provider, or patient, the time to act, through proactive monitoring and evidence-based eye care, is now.

Contact us to learn more 

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>>> Download the GLP-1 and Neuro ebook: The Clinical Imaging Strategy That Safeguards Your Trial's Ocular Endpoints <<<

GLP‑1 Clinical Trial Eye Safety: Summary Table of Key Studies

References

1. Hathaway JT, Shah MP, Hathaway DB, et al. Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide. JAMA Ophthalmol. 2024;142(8):732–739.
2. Shor R, Mihalache A, Noori A, et al. Glucagon-Like Peptide-1 Receptor Agonists and Risk of Neovascular Age-Related Macular Degeneration. JAMA Ophthalmol. Published online June 05, 2025. 
3. Lakhani, Moiz et al. Association of Glucagon-Like Peptide-1 Receptor Agonists With Optic Nerve and Retinal Adverse Events: A Population-Based Observational Study Across 180 Countries. American Journal of Ophthalmology, Volume 277:148-168.
4. Morgenstern AS, Greenspan L, Urbanski C. Clinical Report: Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) and Ocular Health: Guidance for Optometric Practice. American Optometric Association. June, 2025.