Ozempic®: How It Works and the Potential Risks of Vision Loss

Dr. Joseph Rizzo was my mentor at Harvard when I was a young attending. I was very happy to see that he was involved with some of the key studies noting an associated of vision loss with Ozempic®. 

Ozempic® has some positives in terms of helping patients lose weight, but there are some big negatives which include a small risk but devastating concern of vision loss and muscle mass loss.

One of the common questions I get asked now weekly is what is the risk of vision loss with Ozempic®. Here is a more detailed understanding of how Ozempic® works, and what are the key risk. Below references, Dr. Rizzo’s seminal paper as well.

Ozempic® (semaglutide) has gained widespread attention for its effectiveness in managing type 2 diabetes and promoting weight loss. However, recent studies have raised concerns about its potential link to vision loss, particularly through a condition called non-arteritic anterior ischemic optic neuropathy (NAION). In this blog post, we’ll dive into the mechanism of action of Ozempic, explore how it may contribute to vision loss, and outline the associated risks, backed by scientific publications with their authors, publication dates, and sources.

How Ozempic® Works: Mechanism of Action

Ozempic, developed by Novo Nordisk, is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) administered as a once-weekly subcutaneous injection. It is FDA-approved for managing type 2 diabetes and reducing the risk of major cardiovascular events in patients with diabetes and heart disease. It is also used off-label for weight loss, with its sister drug Wegovy® specifically approved for obesity management.

Mechanism of Action

Semaglutide mimics the action of the GLP-1 hormone, which plays a key role in glucose metabolism and appetite regulation. Here’s how it works:

1. Stimulates Insulin Secretion: Semaglutide enhances glucose-dependent insulin release from pancreatic beta cells, helping to lower blood sugar levels in patients with type 2 diabetes. This reduces hyperglycemia without causing significant hypoglycemia, as insulin release is triggered only when blood glucose is elevated.
2. Suppresses Glucagon Release: It inhibits glucagon secretion from pancreatic alpha cells, reducing glucose production in the liver, which further helps control blood sugar.
3. Slows Gastric Emptying: By slowing the movement of food through the stomach, semaglutide promotes satiety, reducing appetite and food intake, which contributes to weight loss.
4. Appetite Suppression: Semaglutide acts on GLP-1 receptors in the hypothalamus, decreasing hunger signals and supporting sustained weight loss.
5. Cardiovascular and Renal Benefits: Beyond glycemic control, semaglutide improves cardiovascular outcomes (e.g., reducing the risk of heart attack or stroke) and may slow the progression of kidney disease in diabetic patients.

These effects make Ozempic highly effective for managing type 2 diabetes and obesity, with clinical trials showing significant reductions in HbA1c (a measure of blood sugar control) and body weight. However, its impact on blood sugar and vascular dynamics may also contribute to ocular complications, as discussed below.

Source: Cigrovski Berkovic M, Strollo F. “Semaglutide-eye-catching results.” PMC, published April 14, 2023.

Vision Loss Risks Associated with Ozempic®

While Ozempic is generally well-tolerated, recent studies have highlighted a potential link to vision loss, primarily through non-arteritic anterior ischemic optic neuropathy (NAION) and worsening of diabetic retinopathy. Below, we explore these risks, their mechanisms, and the evidence supporting them.

1. Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION)

What is NAION? NAION is a rare condition often described as an “eye stroke,” characterized by sudden, painless vision loss in one eye due to reduced or blocked blood flow to the optic nerve. It is the second leading cause of optic nerve-related blindness after glaucoma, affecting up to 10 out of 100,000 people in the general population. The optic nerve, which carries visual signals from the retina to the brain, is highly sensitive to blood flow disruptions, and NAION can result in permanent vision loss with no established treatment.

How Ozempic May Contribute to NAION The exact mechanism linking semaglutide to NAION is not fully understood, but several hypotheses have been proposed:

• Rapid Blood Sugar Changes: Semaglutide’s rapid correction of hyperglycemia may cause fluid shifts in the eye, altering the shape of the lens or affecting optic nerve blood flow. These osmotic changes can lead to temporary blurred vision or, in rare cases, trigger ischemic events in the optic nerve.
• Vascular Effects: GLP-1 receptors are present on the optic nerve, and their activation may influence blood flow patterns, potentially reducing perfusion to the optic nerve in susceptible individuals.
• Crowded Optic Disc (Disc-at-Risk): Patients with a small cup-to-disc ratio (e.g., 0.1, as in a “disc-at-risk”) have a crowded optic nerve head, making them more vulnerable to NAION. Semaglutide’s effects may exacerbate this risk by altering vascular dynamics.

Evidence and Risks

• A study published in JAMA Ophthalmology on July 3, 2024, found that patients with type 2 diabetes prescribed semaglutide were 4.28 times more likely to develop NAION than those on non-GLP-1 diabetes medications, with a cumulative incidence of 8.9% over three years compared to 1.8% in controls. For patients using semaglutide for weight loss, the risk was over seven times higher (6.7% vs. 0.8%). The study analyzed 17,000 patient records from Mass Eye and Ear, prompted by an unusual cluster of three NAION cases in one week among semaglutide users. Authors: Hathaway J, Zekavat SM, and Rizzo JF.
• A December 2024 study from Denmark and Norway, not yet peer-reviewed, confirmed a doubled five-year risk of NAION in diabetic patients using once-weekly semaglutide compared to those on other diabetes drugs. Author: Pottegård A.
• A Johns Hopkins study published in JAMA Ophthalmology in January 2025 (exact date not specified) tracked 37 million people and found a clear link between semaglutide and NAION, particularly in patients with obesity or diabetes. Author: Lincoff N.

Risk for Patients with Glaucoma or Disc-at-Risk

• Glaucoma Patients: Those with glaucoma, who already have optic nerve damage, may face an amplified risk of vision loss from NAION due to their compromised optic nerve health. The combination of glaucoma-related nerve damage and semaglutide’s potential to disrupt optic nerve blood flow could increase the likelihood of severe vision loss.
• Disc-at-Risk (Cup-to-Disc Ratio of 0.1): A small cup-to-disc ratio indicates a crowded optic disc, a known risk factor for NAION. Semaglutide’s vascular or metabolic effects may heighten this risk, with studies suggesting a particularly strong association in patients with this anatomy. The exact risk increase for a 0.1 ratio is not quantified, but the seven-fold risk in obesity patients and four-fold risk in diabetic patients are likely higher in those with a disc-at-risk.

Sources:

• Hathaway J, Zekavat SM, Rizzo JF. “Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide.” JAMA Ophthalmology, July 3, 2024.
• Pottegård A. (Unpublished study, reported in Bloomberg, December 13, 2024).
• Lincoff N. JAMA Ophthalmology, January 2025.

2. Worsening of Diabetic Retinopathy

What is Diabetic Retinopathy? Diabetic retinopathy is a complication of diabetes that affects blood vessels in the retina, potentially leading to vision loss through macular edema, hemorrhages, or neovascularization. Rapid improvements in blood sugar control, as seen with semaglutide, can paradoxically worsen pre-existing retinopathy.

How Ozempic May Contribute

• Rapid Glycemic Control: Semaglutide’s ability to quickly lower blood sugar can disrupt the blood-retinal barrier, increasing vascular endothelial growth factor (VEGF) production and reactive oxygen species (ROS), leading to microvascular changes in the retina.
• Fluid Shifts: Changes in blood glucose levels can alter the eye’s lens shape, causing temporary blurred vision, or exacerbate retinal vascular conditions, worsening retinopathy.

Evidence and Risks

• The SUSTAIN-6 trial, published in 2016, reported a significant increase in diabetic retinopathy complications in patients on semaglutide compared to placebo (50 events in 1,648 patients vs. 29 events in 1,649 patients; hazard ratio 1.76). This was attributed to rapid HbA1c reduction. Authors: Marso SP, Bain SC, Consoli A, et al. New England Journal of Medicine, September 15, 2016.
• A 2023 review noted that while semaglutide does not directly damage the retina, rapid glucose control may exacerbate pre-existing diabetic retinopathy in older patients with long-standing diabetes. Authors: Cigrovski Berkovic M, Strollo F. PMC, April 14, 2023.
• The FDA has noted vision changes as a potential side effect of Ozempic, with 497 reports of blurry vision in the FDA Adverse Events Reporting System (FAERS) as of December 31, 2024.

Risk for Patients with Glaucoma or Disc-at-Risk

• Glaucoma Patients: Those with glaucoma and concurrent diabetes are at higher risk for worsening diabetic retinopathy, which can compound vision loss. The optic nerve damage from glaucoma may also increase susceptibility to further retinal damage.
• Disc-at-Risk: While diabetic retinopathy is less directly linked to a small cup-to-disc ratio, the crowded optic disc may exacerbate vascular complications, potentially increasing the risk of vision loss if retinopathy progresses.

Sources:

• Marso SP, Bain SC, Consoli A, et al. “Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.” New England Journal of Medicine, September 15, 2016不高

6. Age-Related Macular Degeneration (AMD)

What is AMD? Age-related macular degeneration is a retinal condition that can lead to severe vision loss, particularly in older adults. A 2025 study found that GLP-1 RAs like semaglutide may double the risk of neovascular AMD in diabetic patients after six months of use, with a three-fold risk after 30 months, especially in older patients or those with a history of stroke.

How Ozempic May Contribute

• Vascular and Metabolic Effects: Semaglutide’s rapid blood sugar control and potential effects on retinal blood vessels may contribute to the progression of AMD, particularly in patients with pre-existing retinal damage.
• Evidence: A Canadian study published in JAMA Ophthalmology on June 5, 2025, found a doubled risk of neovascular AMD in diabetic patients on semaglutide, with older patients and those with stroke history at higher risk. Authors: Popovic M, VanderBeek B.

Risk for Patients with Glaucoma or Disc-at-Risk

• Glaucoma Patients: The combination of glaucoma and AMD increases the risk of severe vision loss, as both conditions affect the retina and optic nerve.
• Disc-at-Risk: A crowded optic disc may not directly impact AMD risk, but vascular changes induced by semaglutide could exacerbate retinal damage in susceptible individuals.

Source: Popovic M, VanderBeek B. JAMA Ophthalmology, June 5, 2025.

Recommendations for Patients with Glaucoma or Disc-at-Risk

• Regular Eye Exams: Patients with glaucoma or a disc-at-risk (0.1 cup-to-disc ratio) should undergo frequent eye exams, including fundus photography and visual field testing, to monitor for NAION, diabetic retinopathy, or AMD.
• Symptom Vigilance: Sudden vision loss, blurred vision, floaters, or visual field defects require immediate medical attention.
• Risk-Benefit Discussion: Consult with your healthcare provider to weigh Ozempic’s benefits against the risk of vision loss. Alternative medications may be considered for high-risk patients.
• Manage Risk Factors: Control blood pressure, blood sugar, and conditions like sleep apnea to reduce NAION and AMD risk.

Conclusion

Ozempic is a powerful tool for managing type 2 diabetes and obesity, but its potential link to vision loss through NAION, diabetic retinopathy, and AMD raises important considerations, especially for patients with glaucoma or a disc-at-risk. While the absolute risk of these conditions remains low, the relative risk is significant, particularly for those with pre-existing ocular vulnerabilities. Ongoing research is needed to confirm these associations and clarify mechanisms. Patients should work closely with their healthcare providers and ophthalmologists to monitor eye health and make informed treatment decisions.

If you experience vision changes while taking Ozempic, contact your doctor immediately. For more information on Ozempic, visit https://x.ai/grok.

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