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Summary: A new study reveals that patients prescribed semaglutide (Ozempic or Wegovy) for diabetes or weight loss have a higher risk of developing NAION, a potentially blinding eye condition.
Diabetic patients on semaglutide were over four times more likely to be diagnosed with NAION, while overweight patients were over seven times more likely. The findings suggest the need for careful discussions between patients and doctors about this risk. NAION remains a rare but serious condition with no effective treatments.
Key Facts:
Source: Mass General
A new study led by investigators from Mass Eye and Ear found that patients prescribed semaglutide (as Ozempic or Wegovy) for diabetes or weight loss had a higher risk of having a potentially blinding eye condition called NAION than similar patients who had not been prescribed these drugs.
Notably, the study found people with diabetes who had been prescribed semaglutide by their physician and then filled the prescription were more than four times more likely to be diagnosed with NAION. Those who were overweight or had obesity and prescribed this drug were more than seventimes more likely to get the diagnosis.
The study, which was led by Joseph Rizzo, MD, director of the Neuro-Ophthalmology Service at Mass Eye and Ear and the Simmons Lessell Professor of Ophthalmology at Harvard Medical School, published July 3rd in JAMA Ophthalmology.
“The use of these drugs has exploded throughout industrialized countries and they have provided very significant benefits in many ways, but future discussions between a patient and their physician should include NAION as a potential risk,” said Rizzo, the study’s corresponding author.
“It is important to appreciate, however, that the increased risk relates to a disorder that is relatively uncommon.”
NAION is relatively rare, occurring up to 10 out of 100,000 people in the general population. NAION is the second-leading cause of optic nerve blindness (second only to glaucoma) and it is the most common cause of sudden optic nerve blindness. NAION is thought to be caused by reduced blood flow to the optic nerve head, with the consequence of permanent visual loss in one eye.
According to Rizzo, the visual loss caused by NAION is painless and may progresses over many days before stabilizing, and there is relatively little potential for improvement. There are currently no effective treatments for NAION.
The impetus for the study occurred in the late summer of 2023 when Rizzo, a resident (study co-author Seyedeh Maryam Zekavat, MD, PhD) and other Mass Eye and Ear neuro-ophthalmologists noticed a disturbing trend — three patients in their practice had been diagnosed with vision loss from this relatively uncommon optic nerve disease in just one week. The physicians observed all three were taking semaglutide.
This anecdotal recognition led the Mass Eye and Ear research team to run a backward-looking analysis of their patient population to see if they could identify a link between this disease and these drugs, which had been surging in popularity.
Semaglutide was developed to treat type 2 diabetes. The drug encourages weight loss, and its use has snowballed since its launch as Ozempic for diabetes in 2017. The drug was also approved for weight management, branded as Wegovy, and released in 2021.
The researchers analyzed the records of more than 17,000 Mass Eye and Ear patients treated over the six years since Ozempic was released and divided the patients in those who were diagnosed with either diabetes or overweight/ obesity.
The researchers compared patients who had received prescriptions for semaglutide compared to those taking other diabetes or weight loss drugs. Then, they analyzed the rate of NAION diagnoses in the groups, which revealed the significant risk increases.
There are several limitations to the study. Mass Eye and Ear sees an unusually high number of people with rare eye diseases, the study population is majority white, and the number of NAION cases seen over the six-year study period is relatively small. With small case numbers, statistics can change quickly, Rizzo noted.
The researchers also couldn’t determine if the patients actually took their medication or if they started and then stopped taking semaglutide at some point and how this might have impacted their risk.
Importantly, the study does not prove causality, and the researchers don’t know why or how this association exists, and why there was a difference reported in diabetic and overweight groups.
“Our findings should be viewed as being significant but tentative, as future studies are needed to examine these questions in a much larger and more diverse population,” Rizzo said.
“This is information we did not have before and it should be included in discussions between patients and their doctors, especially if patients have other known optic nerve problems like glaucoma or if there is preexisting significant visual loss from other causes.”
Authorship: In addition to Rizzo and Zekavat, other Mass General Brigham co-authors include Jimena Tatiana Hathaway, MD, MPH (MEE); Madhura P. Shah, BS (MEE); David B. Hathaway, MD (BWH); Drenushe Krasniqi, BA (MEE); John W. Gittinger Jr, MD (MEE); Dean Cestari, MD (MEE); Robert Mallery, MD (MEE); Bardia Abbasi, MD (MEE); Marc Bouffard, MD (MEE); Bart K. Chwalisz, MD (MEE) and Tais Estrela, MD (MEE).
Disclosures: No conflicts of interest reported.
Funding: This work was funded in part by a grant from Research to Prevent Blindness.
Author: Tim Sullivan
Source: Mass General
Contact: Tim Sullivan – Mass General
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide” by Joseph Rizzo et al. JAMA Opthalmology
Abstract
Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide
Importance
Anecdotal experience raised the possibility that semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA) with rapidly increasing use, is associated with nonarteritic anterior ischemic optic neuropathy (NAION).
Objective
To investigate whether there is an association between semaglutide and risk of NAION.
Design, Setting, and Participants
In a retrospective matched cohort study using data from a centralized data registry of patients evaluated by neuro-ophthalmologists at 1 academic institution from December 1, 2017, through November 30, 2023, a search for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code H47.01 (ischemic optic neuropathy) and text search yielded 16 827 patients with no history of NAION.
Propensity matching was used to assess whether prescribed semaglutide was associated with NAION in patients with type 2 diabetes (T2D) or overweight/obesity, in each case accounting for covarying factors (sex, age, systemic hypertension, T2D, obstructive sleep apnea, obesity, hyperlipidemia, and coronary artery disease) and contraindications for use of semaglutide.
The cumulative incidence of NAION was determined with the Kaplan-Meier method and a Cox proportional hazards regression model adjusted for potential confounding comorbidities. Data were analyzed from December 1, 2017, through November 30, 2023.
Exposures
Prescriptions for semaglutide vs non–GLP-1 RA medications to manage either T2D or weight.
Main Outcomes and Measures
Cumulative incidence and hazard ratio of NAION.
Results
Among 16 827 patients, 710 had T2D (194 prescribed semaglutide; 516 prescribed non–GLP-1 RA antidiabetic medications; median [IQR] age, 59 [49-68] years; 369 [52%] female) and 979 were overweight or obese (361 prescribed semaglutide; 618 prescribed non–GLP-1 RA weight-loss medications; median [IQR] age, 47 [32-59] years; 708 [72%] female). In the population with T2D, 17 NAION events occurred in patients prescribed semaglutide vs 6 in the non–GLP-1 RA antidiabetes cohort.
The cumulative incidence of NAION for the semaglutide and non–GLP-1 RA cohorts over 36 months was 8.9% (95% CI, 4.5%-13.1%) and 1.8% (95% CI, 0%-3.5%), respectively. A Cox proportional hazards regression model showed higher risk of NAION for patients receiving semaglutide (hazard ratio [HR], 4.28; 95% CI, 1.62-11.29); P < .001). In the population of patients who were overweight or obese, 20 NAION events occurred in the prescribed semaglutide cohort vs 3 in the non–GLP-1 RA cohort.
The cumulative incidence of NAION for the semaglutide vs non–GLP-1 RA cohorts over 36 months was 6.7% (95% CI, 3.6%-9.7%) and 0.8% (95% CI, 0%-1.8%), respectively. A Cox proportional hazards regression model showed a higher risk of NAION for patients prescribed semaglutide (HR, 7.64; 95% CI, 2.21-26.36; P < .001).
Conclusions and Relevance
This study’s findings suggest an association between semaglutide and NAION. As this was an observational study, future study is required to assess causality.