A new study published JAMA Ophthalmology has brought attention to a series of vision problems observed in patients taking semaglutide and tirzepatide, popular drugs for type 2 diabetes and obesity. In this report, nine patients experienced serious eye complications—including seven cases of a condition where reduced blood flow to the optic nerve leads to vision loss, one case of swelling of the optic nerve, and one case affecting the retina. Although the study does not prove these drugs are the direct cause, the findings raise concerns that rapid improvements in blood sugar levels may be linked to these visual issues.
Semaglutide is the active component in Ozempic, Wegovy, and Rybelsus, while tirzepatide is found in Mounjaro and Zepbound. In 2023, nearly two percent of Americans received a prescription for semaglutide.
Semaglutide and tirzepatide are both medications belonging to a class of drugs known as incretin-based therapies. These drugs are widely prescribed to manage type 2 diabetes and obesity. They work by mimicking the actions of natural hormones in the body that are released after eating. Semaglutide primarily acts as an agonist for the glucagon-like peptide 1 (GLP-1) receptor, while tirzepatide acts as an agonist for both the GLP-1 and gastric inhibitory polypeptide (GIP) receptors. By activating these receptors, these medications help to lower blood sugar levels and promote weight loss. They achieve this by increasing insulin release, decreasing glucagon secretion (a hormone that raises blood sugar), slowing down stomach emptying, and reducing appetite.
The motivation for this recent study arose from a concerning clinical observation made by Bradley J. Katz of the John A. Moran Eye Center at University of Utah Health. Katz encountered a patient who experienced sudden vision loss shortly after starting semaglutide. What was particularly striking was that when the patient, upon medical advice, restarted the medication after a brief pause, a similar vision problem occurred in the other eye.
This unusual and sequential pattern of vision loss in direct temporal proximity to semaglutide use raised a red flag for Katz. He recognized the need to investigate whether this was an isolated incident or if there might be a broader, previously unrecognized link between these increasingly popular medications and specific eye complications. This initial patient case served as the catalyst for a wider inquiry into the potential ocular side effects associated with semaglutide and similar drugs like tirzepatide.
Katz initiated an informal inquiry. He posted a description of this patient’s case on NANOSnet, an online forum used by members of the North American Neuro-Ophthalmology Society. This professional network comprises over 800 neuro-ophthalmologists who share clinical experiences and discuss challenging cases. Dr. Katz’s query specifically asked if any other neuro-ophthalmologists had observed similar eye complications in patients taking semaglutide or tirzepatide.
The outreach through NANOSnet proved fruitful. In response to Katz’s query, four neuro-ophthalmologists reported seeing patients with ocular complications who were also using either semaglutide or tirzepatide. In addition to this listserv inquiry, Katz also consulted the National Registry of Drug-Induced Ocular Side Effects to identify any previously reported cases linking these medications to eye problems.
Through these combined methods – the initial case observation, the professional network query, and the registry search – the researchers compiled a total of nine cases that formed the basis of their study. Seven of these patients were diagnosed with nonarteritic anterior ischemic optic neuropathy, a condition where blood flow to the optic nerve is suddenly reduced, leading to damage. One patient was diagnosed with papillitis, which is inflammation of the optic nerve. The final patient was diagnosed with paracentral acute middle maculopathy, a condition affecting the central retina, the light-sensitive tissue at the back of the eye.
For each patient, the researchers collected detailed information. This included their age, sex, the specific medication they were taking (semaglutide or tirzepatide), how long they had been taking it, their history of vascular risk factors like diabetes and high blood pressure, and the specifics of their eye condition. They noted whether the optic nerve swelling was in one or both eyes, whether the vision loss was painful or occurred upon waking, and the degree of visual impairment. They also looked at the cup-disc ratio, a measure of the optic nerve’s appearance, and used imaging techniques like magnetic resonance imaging to visualize the optic nerve and brain.
In some cases, they also performed visual field tests to map out areas of vision loss and blood tests to rule out other potential causes. The study was conducted in accordance with ethical guidelines for human research, ensuring patient privacy and the responsible use of medical information.
The analysis of these nine cases revealed several notable patterns. Among the seven patients with nonarteritic anterior ischemic optic neuropathy, some experienced typical symptoms like sudden, painless vision loss in one eye upon waking. These patients also showed optic nerve swelling and characteristic visual field defects. Imaging in these cases often confirmed the optic nerve abnormalities.
However, some cases presented in less typical ways. For instance, one patient experienced vision problems in both eyes sequentially, linked to starting and restarting semaglutide. Two other patients showed swelling in both optic nerves at the initial examination, and one patient experienced a gradual worsening of vision over several weeks. The patient with papillitis showed sequential swelling in each optic nerve at different times. The patient with paracentral acute middle maculopathy experienced a shadow in their vision, and specialized retinal imaging confirmed damage to the inner layers of the retina.
Importantly, the researchers considered possible explanations for these eye conditions in patients taking semaglutide or tirzepatide. They noted that rapid improvement in blood sugar control, which is a known effect of these medications, might play a role. It is thought that quickly lowering blood sugar levels could potentially lead to optic nerve swelling and subsequent damage in susceptible individuals.
This idea is supported by previous findings linking rapid blood sugar correction to papillitis and by the observation of bilateral optic nerve swelling in some of the reported cases. While other medications have been linked to nonarteritic anterior ischemic optic neuropathy, none of the patients in this series were taking these other drugs, making the potential association with semaglutide and tirzepatide more noteworthy.
The researchers acknowledged that their study has limitations. As a case series, it describes a group of patients but lacks a comparison group of individuals taking these medications who did not develop eye problems. This absence of a control group, along with the retrospective nature of the data collection, means that it is impossible to definitively prove that semaglutide or tirzepatide caused these eye conditions.
“This review was not conducted in any way that we can say these drugs caused the complications,” said Katz. “Further studies are needed to test our hypothesis. However, this is an important issue for ophthalmologists as we monitor the usage of these drugs and how to best be in communication with our patients about them.”
With these medications becoming more widely used to manage type 2 diabetes and obesity, the researchers said it is essential for both doctors and patients to be aware of the potential for serious eye complications. Patients who notice any sudden changes in their vision, such as blurring or loss of vision upon waking, should seek an eye examination as soon as possible. Early detection of problems may allow for adjustments in treatment that could help protect the eyes from further damage.
“The message to the patient is that we are still investigating if these drugs put them at higher risk of ischemic optic nerve damage,” said Norah S. Lincoff, a co-author on the paper and professor of neurology in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo. “The message to the primary care provider is, if a patient on one of these medications calls you and says that there is blurring or vision loss, have them see their ophthalmologist as soon as possible. Don’t wait. Maybe it’s a fluctuation in glucose or it could be something more serious.”
The study, “Ophthalmic Complications Associated With the Antidiabetic Drugs Semaglutide and Tirzepatide,” was authored by Bradley J. Katz, Michael S. Lee, Norah S. Lincoff, Anne S. Abel, Somya Chowdhary, Brian D. Ellis, Ahmad Najafi, John Nguyen, Meagan D. Seay, and Judith E. A. Warner.
