Summary: Researchers identified a small but statistically measurable increase in the risk of a rare, potentially permanent vision-threatening condition—ischemic optic neuropathy—among adults who began treatment with GLP‑1 receptor agonists compared with patients on other standard diabetes medications.
Key Facts
- Absolute risk increase: The added risk is very small: roughly 3 to 4 extra cases of ischemic optic neuropathy per 10,000 patients treated with GLP‑1 receptor agonists over an 18‑month period.
- What ischemic optic neuropathy is: This condition reflects a sudden reduction in microvascular blood flow to the optic nerve. More than 80% of reported events fit the pattern of non‑arteritic anterior ischemic optic neuropathy (NAION).
- How vision is affected: Rather than causing total blindness, the typical presentation is sudden, painless blurring, dimming, or a localized loss of part of the visual field (commonly altitudinal defects) in one eye.
- Recovery and permanence: Visual loss from NAION is generally permanent. About one‑third of patients may regain some vision within the first six months, but most retain lasting deficits or blind spots.
- Higher‑risk groups: Most events in the study occurred in men and in people aged roughly 50 to 65 years.
- Association, not proven causation: The lead investigator, Dr. Chintan Dave, emphasizes that this registry‑based observational study shows a statistical association but does not establish direct cause‑and‑effect. The observed link could reflect unmeasured differences in baseline vascular health, longer diabetes duration or severity, or other diabetic complications rather than a direct toxic effect of GLP‑1 drugs.
Source: Rutgers University
A widely prescribed class of medications for type 2 diabetes and obesity—glucagon‑like peptide‑1 receptor agonists (GLP‑1 RAs)—was associated with a small increase in risk for ischemic optic neuropathy, a rare condition that can cause sudden vision loss, according to researchers at Rutgers.
The study, published in the Annals of Internal Medicine, analyzed a large U.S. commercial claims database covering adults aged 18 to 65 with type 2 diabetes who began treatment with GLP‑1 RAs or with alternative glucose‑lowering medications.
Common GLP‑1 agents include semaglutide (marketed as Ozempic and Wegovy) and tirzepatide (marketed as Mounjaro and Zepbound). These drugs can reduce cardiovascular and kidney disease risk in people with metabolic disease, but large‑scale safety monitoring continues to explore uncommon adverse events.
In the Rutgers analysis, GLP‑1 users had higher 18‑month rates of ischemic optic neuropathy than users of sodium–glucose cotransporter‑2 inhibitors (SGLT2is) or dipeptidyl peptidase‑4 inhibitors (DPP4is), although the absolute event rate remained low.
“Ischemic optic neuropathy is uncommon, but clinically important because it can cause sudden, potentially permanent vision loss,” said Chintan Dave, associate professor at the Ernest Mario School of Pharmacy and lead author. “The additional risk we found was small—about three to four additional cases per 10,000 patients over 18 months—but clinicians and patients should be aware of this possible association.”
Researchers note that the growing use of GLP‑1 medications, including among people without diabetes, makes careful surveillance of rare adverse events essential.
Dave added that most events occurred in people older than 50 and in men, and that early recognition of warning symptoms and prompt ophthalmologic evaluation may be particularly important for patients already at higher baseline vascular or eye disease risk.
More than four out of five cases in the study were estimated to represent the non‑arteritic anterior form of ischemic optic neuropathy. Although around one‑third of affected patients may recover some vision—typically within the first six months—most retain some permanent deficit such as a blind spot or reduced acuity. The condition usually causes localized field loss rather than total blindness.
The authors caution that residual confounding is possible: diagnostic codes specific to NAION were not available, and clinical variables like body mass index and duration of diabetes were missing from claims data. These limitations mean the association could reflect differences in patients’ underlying health rather than a direct effect of GLP‑1 drugs. Additional controlled and biochemical studies are needed to clarify mechanisms and causality.
Coauthors include Kamika Reynolds, Kimberly O’Malley, and Jason Roy.
Key Questions Answered
A: Ischemic optic neuropathy is like a “stroke” of the optic nerve. It happens when small blood vessels supplying the front of the nerve become suddenly restricted, depriving tissue of oxygen. It typically causes sudden, painless blurring, dimming, or a persistent shadow that removes a portion of the visual field (for example, the top or bottom half) in one eye, rather than complete darkness in both eyes.
A: No. The absolute additional risk identified is very low—about 3 to 4 extra cases per 10,000 patients over 18 months. For most patients, the significant benefits of GLP‑1 therapies—weight reduction, improved glycemic control, and lower risks of heart and kidney complications—outweigh this rare potential risk. Any change in medication should be made only after discussion with a treating clinician.
A: No. This observational, registry‑based analysis demonstrates a statistical association but cannot prove causation. The modest increase in events may reflect preexisting vascular risk or more advanced metabolic disease in patients prescribed GLP‑1 agents. Further controlled research is required to determine whether there is a direct biological effect.
Editorial Notes
- Article edited by a Neuroscience News editor.
- The journal article was reviewed in full.
- Additional context added by staff.
About this research
Author: Patti Zielinski
Source: Rutgers University
Contact: Patti Zielinski – Rutgers University
Image credit: Neuroscience News
Original research: Open access. “Glucagon‑Like Peptide‑1 Receptor Agonists and Risk for Ischemic Optic Neuropathy: A Target Trial Emulation” by Kamika R. Reynolds, Kimberly M. O’Malley, Jason A. Roy, and Chintan V. Dave. Annals of Internal Medicine. DOI: 10.7326/ANNALS-25-00860
Abstract
Glucagon‑Like Peptide‑1 Receptor Agonists and Risk for Ischemic Optic Neuropathy: A Target Trial Emulation
Background:
Data are limited on the relationship between GLP‑1 receptor agonists and nonarteritic anterior ischemic optic neuropathy (NAION), which makes up the majority of ischemic optic neuropathy cases in adults.
Objective:
Estimate the effect of GLP‑1 receptor agonists versus SGLT2 inhibitors and DPP‑4 inhibitors on the risk of ischemic optic neuropathy.
Design and setting:
An observational emulation of a target trial using a large U.S. commercial claims database spanning January 2017 to December 2022.
Participants:
Adults aged 18–65 years with type 2 diabetes who initiated a GLP‑1 receptor agonist, an SGLT2 inhibitor, or a DPP‑4 inhibitor.
Measurements:
The primary outcome was incident ischemic optic neuropathy (used as a proxy for NAION). Analyses adjusted for more than 80 covariates with inverse probability of treatment weighting; 18‑month cumulative incidence and risk differences per 10,000 patients were calculated.
Results:
At 18 months, ischemic optic neuropathy risk was 8.5 versus 5.5 per 10,000 among GLP‑1RA users compared with SGLT2i users (risk difference 3.0 per 10,000; 95% CI, 0.4 to 5.7), and 7.8 versus 4.2 per 10,000 compared with DPP4i users (risk difference 3.6; 95% CI, 1.1 to 6.1). Numbers needed to harm were 3,333 and 2,778, respectively. Most events occurred in people older than 50 and in men. Risk differences were larger in those with cardiovascular disease or preexisting eye conditions and smaller among younger patients and women. Differences were reduced among patients using metformin alone versus those on two or more diabetes medications.
Limitations:
Specific diagnostic codes for NAION were not available. Missing clinical data (for example, BMI and diabetes duration) may lead to residual confounding, leaving uncertainty about causality.
Conclusion:
Use of GLP‑1 receptor agonists was associated with a higher 18‑month risk of ischemic optic neuropathy compared with SGLT2 and DPP‑4 inhibitors, but the absolute risk remained very low and observed differences may reflect residual confounding.
Primary funding source:
National Institutes of Health.