Case Series Shows Possible Link Between Semaglutide, Ophthalmic Complications

Results from a case series identified a potential association between ophthalmic complications and the rapid correction of hyperglycemia, brought on by patients using either semaglutide or tirzepatide. These complications are potentially separate from the toxic effect of the drugs, according to the study published in JAMA Ophthalmology.1

Patients can use semaglutide and tirzepatide as means of treating both type 2 diabetes and obesity through the use of glycemic control. The previous SUSTAIN 6 trial of patients with type 2 diabetes (T2D) using semaglutide were found to have worsened diabetic retinopathy when using semaglutide,2 making its potential as an exacerbator important for study. This study aimed to describe patients using semaglutide or tirzepatide who were diagnosed with ophthalmic complications while using the drug.

Further study will be needed to confirm the possible association between ocular complications and semaglutide | Image credit: Starmarpro - stock.adobe.com

Cases were collected through a query conducted by the authors of the study. Neuro-ophthalmologists who were listed in the NANOSnet database that was available to members of the North American Neuro-Ophthalmology Society were questioned about any cases of ophthalmic complications involving patients using semaglutide or tirzepatide. The author also included a query into the National Registry of Drug-Induced Ocular Side Effects. There were 4 neuro-ophthalmologists who reported cases of complications surrounding the eye when a patient used the drug. Only 1 case was reported to the Registry.

There were 9 patients included in this study. The mean (SD) age of the participants was 57.4 (11.6) years and 5 of the patients were women. There were 7 cases of nonarteritic anterior ischemic optic neuropathy (NAION) in patients who had not previously used any drug associated with optic neuropathies or retinopathies within a year of symptom onset.

The first patient, a woman in her 50s, received insulin and semaglutide for 4 days before a subcutaneous dose of semaglutide. She awoke with vision loss in the left eye and stopped taking the medication. The patient began taking the medication again after 2 months of recovery and had another vision loss episode 2 weeks after administering a second subcutaneous dose of semaglutide. A perimetry found bilateral, superior altitudinal defects.

A man in his 60s experienced painless blurred vision after taking semaglutide for 10 months and increasing his dosage 6 months prior. The man reported symptomatic vision loss in his left eye 4 months after the initial presentation. Vision loss stopped progressing after semaglutide was discontinued. A woman in her 30s with a history of T2D reported shadows in her right eye after taking semaglutide for 3 months. Diffuse pallor was reported after a month, soon after semaglutide was discontinued for an unrelated reason.

A man in his 50s with a history of T2D reported linear scotoma in his left eye after taking semaglutide orally for 1 year. Pallor was reported after 1 month but vision had stabilized and semaglutide was discontinued. Another man in his 60s with a history of T2D reported a painless shade in his left eye after taking tirzepatide for 1 year through subcutaneous injections. He was diagnosed with NAION and continued to use tirzepatide.

A man in his 60s with a history of T2D reported vision loss in his left eye approximately 4 months after increasing his dose of tirzepatide, which he had been taking for a year at that point. Although his left optic nerve was swollen, the patient continued to use tirzepatide. A woman in her 50s reported vision loss after starting subcutaneous tirzepatide 5 months earlier. Tirzepatide was discontinued and her optic nerve swelling resolved.

A woman in her 40s with T2D had right optic nerve swelling after starting subcutaneous semaglutide. The woman was diagnosed with stage 2 to 3 edema in her left eye but continued to use semaglutide. Optic nerve swelling resolved after 1 year. A woman in her 70s who had been using semaglutide for 1 year presented with symptoms of paracentral acute middle maculopathy and her optical coherence tomography was unchanged after 3 months.

There are a few limitations to this study. The data presented are all from case studies, which could lead to incomplete or inaccurate data which prevents the ability to determine causality. This is due to the lack of control group, reliance on historical data, and any potential selection bias. A study with a broader scope and more participants will be needed in the future to confirm these findings.

Although a causal link could not be inferred from the data in the case series, the researchers have hypothesized “that rapid correction of hyperglycemia induced by these drugs, rather than a toxic effect of the drugs, could be associated with the ophthalmic complications reported.”

References

1. Katz BJ, Lee MS, Lincoff NS, et al. Ophthalmic complications associated with the antidiabetic drugs semaglutide and tirzepatide. JAMA Ophthalmol. Published online January 30, 2025. doi:10.1001/jamaophthalmol.2024.6058
2. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834-1844. doi:10.1056/NEJMoa1607141