Summary: Researchers unmasked a slight, statistically measurable increase in the risk of developing a rare, potentially permanent blinding condition known as ischemic optic neuropathy (a sudden restriction of blood flow to the optic nerve) among patients initiating GLP-1 therapy compared to standard diabetes regimens.
Key Facts
- The Absolute Risk Expansion: The calculated increase in absolute risk is remarkably small, manifesting as approximately 3 to 4 additional cases of ischemic optic neuropathy per 10,000 patients treated with GLP-1 receptor agonists over a standard 18-month therapeutic window.
- The Nature of Ischemic Optic Neuropathy: The condition involves a sudden, sharp restriction of microvascular blood flow supplying the optic nerve. More than 80% of these occurrences manifest as non-arteritic anterior ischemic optic neuropathy (NAION).
- Visual Field Degradation Characteristics: Rather than triggering absolute darkness or total blindness, the condition typically presents as sudden blurring, dimming, or a localized loss of a specific part of the visual field (altitudinal defects) in one eye.
- Permanence and Recovery Limits: Visual deficits resulting from NAION are usually permanent. While approximately one-third of diagnosed individuals experience mild visual improvement within the initial six months, the vast majority are left with lasting structural blind spots or reduced acuity.
- High-Risk Demographic Targets: The vast majority of patients within the study who experienced active ischemic events fell into specific baseline sub-groups: predominantly men, or individuals between the ages of 50 and 65.
- Association vs. Direct Causation: Dr. Chintan Dave explicitly emphasizes that because this is a registry-based observational study, it demonstrates a clear statistical association but does not prove direct cause-and-effect. The detected correlation may alternatively stem from unmeasured variations in patients’ baseline vascular health, advanced metabolic severity, or underlying diabetic complications, rather than a direct cellular effect of the GLP-1 molecules themselves.
Source: Rutgers
A medication commonly used to treat Type 2 diabetes and obesity was associated with a slight increase in risk for a rare condition involving reduced blood flow to the optic nerve that can cause sudden vision loss, according to Rutgers researchers.
Their study, published in Annals of Internal Medicine, examined data from a large database of United States adults ages 18 to 65 with Type 2 diabetes who started taking medication to treat the condition, including glucagon-like peptide-1 receptor agonists, or GLP-1s.
GLP-1s, such as semaglutide (sold as Ozempic and Wegovy) and tirzepatide (sold as Mounjaro and Zepbound), are commonly used to treat Type 2 diabetes and obesity and can reduce cardiovascular and kidney disease risks, but researchers still are exploring potential risks of these medications.
Researchers found an association between the use of GLP-1s and a higher risk for the condition, called ischemic optic neuropathy, although the risk remained low.
“Although ischemic optic neuropathy was rare, it is clinically important because it can involve sudden vision loss,” said Chintan Dave, a core faculty member of the Center for Pharmacoepidemiology and Treatment Science at Rutgers Institute for Health, Health Care Policy and Aging Research. “The increase in risk was small – approximately three to four additional cases per 10,000 patients treated with GLP-1s over 18 months, but clinicians and patients should be aware of this potential association.”
Researchers said while the risk is low, the rising use of GLP-1s in patients with and without Type 2 diabetes warrants special attention to medication safety.
“Most patients in our study who had ischemic optic neuropathy were either men or men and women aged 50 to 65,” said Dave, an associate professor at the Ernest Mario School of Pharmacy and the lead author of the study. “Because ischemic optic neuropathy can present with sudden vision loss, which may be permanent, early recognition of symptoms and prompt ophthalmologic evaluation may be especially important for patients at higher baseline risk.”
More than four in five cases of ischemic optic neuropathy are estimated to be the non-arteritic anterior form. This type of vision loss is usually permanent, although approximately one-third of patients may experience some improvement, generally within the first six months, Dave said. Even when vision improves, some deficit often remains. The condition typically causes blurring, dimming or loss of part of the visual field in one eye rather than complete blindness or total darkness.
Researchers said the findings may reflect differences in patients’ underlying health, rather than a direct effect of the medications. They added that more research is needed to determine causation.
Coauthors of the study include Kamika Reynolds and Kimberly O’Malley of the Institute for Health and Jason Roy of the Rutgers School of Public Health.
Key Questions Answered:
A: Ischemic optic neuropathy is essentially a “stroke” of the optic nerve, the vital cable that transmits visual data from the eye to the brain. It occurs when the tiny blood vessels supplying the front part of the nerve suddenly become restricted or blocked, starving the nerve tissue of oxygen. Instead of causing complete blindness or total darkness, it usually results in sudden, painless blurring, dimming, or a persistent shadow that cuts off a specific part of the visual field (like losing the top half or bottom half of your vision) in one eye.
A: Absolutely not. The absolute risk discovered by the Rutgers pharmacoepidemiology team remains incredibly low, affecting only about 3 to 4 extra people out of every 10,000 patients treated over a year and a half. For the vast majority of patients, the immense, proven systemic benefits of GLP-1 medications, such as reversing severe obesity, stabilizing high blood sugar, reducing the risk of stroke, and preventing kidney failure, far outweigh this rare visual side effect. Any changes to a treatment plan must be discussed directly with a primary care physician.
A: No, it does not show direct cause-and-effect. Dr. Chintan Dave notes that this study highlights a statistical association based on large-scale health data. It is entirely possible that the slight rise in optic nerve issues reflects the underlying, advanced vascular damage or high baseline cardiovascular strains already present in patients who require these stronger medications, rather than a direct toxic effect of the drug molecules themselves. Further controlled biochemical research is required to definitively solve the underlying biological mechanism.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this GLP1s and vision loss research news
Author: Patti Zielinski
Source: Rutgers University
Contact: Patti Zielinski – Rutgers University
Image: The image is credited to 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, MS, PhD, Kimberly M. O’Malley, MS, Jason A. Roy, PhD, and Chintan V. Dave, PharmD, PhD. 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:
There are few data evaluating the association between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and nonarteritic anterior ischemic optic neuropathy (NAION), which constitutes approximately 75% of ischemic optic neuropathy (ION) cases in adults.
Objective:
To estimate the effect of GLP-1RAs versus sodium–glucose cotransporter-2 inhibitors (SGLT2is) and dipeptidyl peptidase-4 inhibitors (DPP4is) on risk for ION.
Design:
Observational emulation of a target trial.
Setting:
Large U.S.-based commercial claims database (January 2017 to December 2022).
Participants:
Patients aged 18 to 65 years with type 2 diabetes initiating a GLP-1RA, an SGLT2i, or a DPP4i.
Measurements:
The primary outcome was incident ION as a proxy for NAION. Analyses adjusted for more than 80 covariates using inverse probability of treatment weights, and 18-month cumulative incidence and risk differences (RDs) per 10 000 patients were estimated.
Results:
The 18-month risk for ION was 8.5 versus 5.5 per 10 000 among GLP-1RA users versus SGLT2i users (RD, 3.0 [95% CI, 0.4 to 5.7]) and 7.8 versus 4.2 per 10 000 among GLP-1RA users versus DPP4i users (RD, 3.6 [CI, 1.1 to 6.1]). Corresponding numbers needed to harm were 3333 and 2778, respectively. Among GLP-1RA users, 69 (85.2%) of the 81 ION events occurred in persons older than 50 years and 57 (70.3%) occurred in men. Risk differences were attenuated among metformin monotherapy users (2.0 and 4.1) compared with users of 2 or more diabetes medications (5.7 and 4.0) versus SGLT2is and DPP4is, respectively. Risk differences were higher in men, patients aged 50 years or older, and those with cardiovascular disease or ophthalmic conditions, with minimal differences in women and those younger than 50 years.
Limitations:
Diagnostic codes specifically for NAION were lacking. Missing data on key clinical factors (such as body mass index and type 2 diabetes duration) may contribute to residual confounding, leaving uncertainty about whether the observed association is causal.
Conclusion:
Use of GLP-1RAs was associated with higher 18-month risk for ION than use of SGLT2is and DPP4is, although absolute risk remained very low. Observed differences may reflect residual confounding.
Primary Funding Source:
National Institutes of Health.
