New research links two widely used diabetes drugs, semaglutide or tirzepatide, to a rare but potentially vision-threatening eye condition, raising questions about drug-specific risks and the need for closer monitoring.
Study: Semaglutide or Tirzepatide and Optic Nerve and Visual Pathway Disorders in Type 2 Diabetes. Image credit: Vince Scherer/Shutterstock.com
A study published in JAMA Network Open reported that treatment with antidiabetic medicines semaglutide and tirzepatide increases the risk of optic neuropathy and other optic nerve disorders in patients with type 2 diabetes.
Background
Glucagon-like peptide-1 receptor agonists (GLP-1RA) are a group of medications widely used to treat diabetic or obese individuals. These medications have high potential to reduce diabetes-related complications, including cardiovascular and nephrological disorders.
Semaglutide and tirzepatide are second-generation GLP-1RA medications approved by the U.S. Food and Drug Administration (FDA) for treating diabetes and obesity. However, these medications are associated with adverse side effects, including gastrointestinal disorders, thyroid C-cell tumors, and pancreatitis.
Some recent studies have linked semaglutide and tirzepatide with increased risk of nonarteritic anterior ischemic optic neuropathy. However, the reported associations are inconclusive, and it largely remains unknown whether these medications are associated with an increased risk of other optic nerve disorders.
In the current study, researchers investigated the associations between treatment with either semaglutide or tirzepatide and the risk of optic nerve and visual pathway disorders in patients with type 2 diabetes.
Nonarteritic anterior ischemic optic neuropathy is characterized by loss of vision due to impaired blood flow to the optic nerve. The condition is more prevalent among patients with diabetes, obesity, hypertension, hyperlipidemia, cerebrovascular disease, and obstructive sleep apnea.
Study design
The study used a nationwide, multicenter database of electronic health records of more than 118 million US patients to compare semaglutide or tirzepatide with other antidiabetic medications for the associated risk of optic nerve and visual pathway disorders in patients with type 2 diabetes.
The target population in the database was type 2 diabetes patients with no prior diagnosis of eye disorder, who were consuming semaglutide, tirzepatide, or other GLP-1RA and non-GLP-1RA antidiabetic medications.
Key findings
The analysis of electronic health records revealed that about 0.04% of patients who were treated with either semaglutide or tirzepatide had developed nonarteritic anterior ischemic optic neuropathy over two years, as compared to 0.02% of patients who were treated with other antidiabetic medications.
The prevalence of other optic nerve disorders was 0.12% among semaglutide- or tirzepatide-treated patients, compared to 0.07% among patients receiving non-GLP-1RA antidiabetic medications.
Compared to other GLP-1RAs, semaglutide or tirzepatide was associated with a significantly increased risk of other optic nerve disorders; the increased risk of NAION was directionally higher but did not reach statistical significance.
Study significance
The study finds that compared to other antidiabetic medications, treatment with either semaglutide or tirzepatide is associated with an increased risk of nonarteritic anterior ischemic optic neuropathy and other optic nerve disorders. However, the overall risk is low.
The study could not find any association between treatment with semaglutide or tirzepatide and risk of optic neuritis, papilledema, or optic atrophy, compared with all other antidiabetic medications. However, in a head-to-head versus other GLP-1RAs, there was a significant association with other optic disc disorders. This lack of association might be due to the distinct pathophysiology of each optic nerve and visual pathway disorder.
Notably, the study reports that treatment with either semaglutide or tirzepatide is consistently associated with an increased risk of developing optic nerve disorders. Another notable finding is that compared to other GLP-1RAs, semaglutide or tirzepatide is associated with increased risks of optic neuropathy and other optic nerve disorders. These patterns suggest, although do not prove, that the observed associations may be specific to these two medications rather than the GLP-1RA class as a whole.
A direct influence of GLP-1RAs can be expected as GLP-1 receptors are expressed in the optic nerve. However, these findings suggest that the observed associations might also involve indirect links with abrupt changes in metabolic parameters. Further studies are needed to replicate these findings, explore underlying mechanisms, and identify individuals with higher susceptibility to these potential complications.
Due to the observational study design, the study could not determine the causality of observed associations. Moreover, the study observations are based on patients’ electronic health reports, which have their limitations of unmeasured or uncontrolled confounding and biases.
The study involved patients with type 2 diabetes who were followed up for two years. The study used International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) code H47.01, “ischemic optic neuropathy” for nonarteritic anterior ischemic optic neuropathy diagnosis, as no specific ICD-10 code is available for this disease. ICD-10–based diagnoses may have some limitations due to overdiagnosis, misdiagnosis, and underdiagnosis. Furthermore, due to data inaccessibility, the researchers could not manually review patient-level data to confirm disease diagnosis.
The researchers analyzed general and specific ICD-10 disease codes to systematically identify the associations of semaglutide or tirzepatide with optic nerve and visual pathways. They observed that these two medications are preferably associated with optic nerves but not other visual pathways. These findings provide a foundation for future research to focus on specific eye disorders.
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