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 US population was prescribed GLP-1 in 2024, roughly 15 million people.
As social media celebrates before-and-after photos, it’s no wonder clinics struggle to keep them in stock. However, lost in the excitement is a growing and concerning issue that deserves 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
- 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.
- 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]
- 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 aren’t isolated case reports. They represent thousands of patients from dozens of countries and a consistent pattern of vision-threatening events.
What This Means 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 play a critical role in detecting and mitigating potentially irreversible eye damage in GLP-1 patients.
What We Can Do Right Now
At 20/20 Onsite, we bridge the gap between systemic care and vision protection. Our Mobile Vision Clinics (MVCs) and clinical research infrastructure bring ophthalmic expertise and clinical trial solutions directly to the point of need.
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. That would equate to an absolute tragedy in the age of modern 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. Their benefits are real. But no drug is above scrutiny. At 20/20 Onsite, we believe your vision is worth protecting, and we’re here to help you do just that.
Whether you’re a researcher, physician, or patient, the time to act is now.
Explore the latest research summary
GLP‑1 Clinical Trial Eye Safety: Summary Table of Key Studies
Study |
Findings |
Methodology |
BMC Medicine, 2025 (Massy et al.) |
Semaglutide had higher vision impairment reporting vs other GLP-1 RAs and antidiabetics (rOR 1.95–3.89). |
FAERS disproportionality analysis (n=302,706 reports) |
JAMA Ophthal., 2024 (Hathaway et al.) |
Two-fold to seven-fold increased NAION risk in semaglutide users. |
Single-center retrospective cohort (n=1,689) |
JAMA Ophthal., 2025 (Shor et al.) |
>2x increased nAMD risk in GLP-1 RA users; dose–response with exposure duration. |
Population-based cohort (n=139,002) |
Am J Ophthal., 2025 |
Global FAERS/VigiBase analysis: high ROR for optic nerve & retinal AEs with semaglutide. |
Disproportionality in two large databases |
JAMA Ophthal., 2025 (Katz et al.) |
Case series: 7 NAION, 1 papillitis, 1 PAMM with semaglutide/tirzepatide. |
Retrospective case series (n=9) |
NEJM, 2016 (Marso et al.) |
Semaglutide ↑ DR complications vs placebo (3.0% vs 1.8%; HR 1.76). |
Phase 3 CVOT (SUSTAIN 6; n=3,297) |
Diabetes Care, 2021 (Bethel et al.) |
Meta-regression: early HbA1c reduction predicts DR progression across GLP-1 RAs. |
Meta-analysis of CVOTs |
Diabetes Metab J, 2023 (Lin et al.) |
GLP-1 RA users ↑ PDR & DME progression vs SGLT-2I users (HR 1.45). |
Nationwide retrospective cohort |
Int J Mol Sci, 2022 (Puddu & Maggi) |
GLP-1RAs exhibit anti-inflammatory retinal effects; clinical trials show mixed DR signals. |
Preclinical models & clinical data |
References
- 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.
- 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.
- 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.
- 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.