The seizure-preventive effect of the diabetes and obesity drug ‘semaglutide’ has been confirmed. Provided by Getty Images Bank.
Semaglutide, a diabetes and obesity medication sold under brand names such as Wegovy and Ozempic, has been shown in a large-scale study to significantly reduce the risk of seizures that first occur in adulthood. The findings suggest that semaglutide may help protect brain health.
Seoul National University Hospital announced on the 23rd that a joint research team led by Professors Jang Yoon-hyuk and Lee Soon-tae of the National Strategic Technology Specialized Research Institute and the Department of Neurology, Professor Eun Yong of the Department of Internal Medicine at Columbia University in the United States, and PhD candidate Bong Su-hwan of the Harvard T.H. Chan School of Public Health analyzed the association between semaglutide use and adult-onset seizures and published the results in the latest issue of Neurology, the journal of the American Academy of Neurology.
Adult-onset seizure refers to a seizure that occurs for the first time after the age of 18. New-onset seizures, especially in middle-aged and older adults, can be associated with acquired brain injuries such as stroke, neurodegenerative diseases, and traumatic brain injury, making them an important indicator of brain health.
When a seizure occurs, the risk of falls increases, and driving and social activities become restricted, greatly affecting patients’ functional outcomes and quality of life. Current treatment focuses on preventing recurrence with antiseizure medications after a seizure has already occurred. There is still no fundamental treatment strategy that prevents seizures themselves.
Semaglutide is a therapy that has demonstrated disease-protective effects in multiple domains. The American Diabetes Association recommends it as a first-line treatment for patients with type 2 diabetes who are at high risk of cardiovascular disease, and it is also used for blood glucose and obesity management, chronic kidney disease, and metabolic dysfunction-associated steatohepatitis (MASH)
The research team used electronic medical record (EMR) data from the U.S. National Institutes of Health (NIH) large-scale health care cohort ‘All of Us Program’ to analyze the impact of semaglutide on seizures.
The researchers first identified 69,228 patients with type 2 diabetes and then analyzed the risk of adult-onset seizures among 18,243 adult patients aged 18 or older who were newly prescribed semaglutide, other glucose-lowering agents, or SGLT2 inhibitors (antidiabetic drugs).
To ensure accurate comparisons, they adopted a ‘target trial emulation’ method that mimics a clinical trial. Patients were assigned to a semaglutide vs. other glucose-lowering agent comparison group (10,213 patients) and a semaglutide vs. SGLT2 inhibitor comparison group (8,605 patients). Drug effects were then analyzed after finely adjusting for clinical differences such as age, comorbidities, and body mass index.
As a result, the newly initiated semaglutide group had about a 56% lower risk of adult-onset seizures compared with the group receiving other glucose-lowering agents. The ‘4-year cumulative risk difference,’ which represents the difference in the proportion of patients who actually experienced seizures, was found to be 1.78 percentage points. In the comparison with SGLT2 inhibitors, the semaglutide group showed about a 52% lower seizure risk, with a 4-year cumulative risk difference of 1.46 percentage points.
When translated into the number of patients needing treatment, substituting semaglutide for other glucose-lowering agents would prevent one additional seizure for every 70 patients treated, and substituting semaglutide for SGLT2 inhibitors would prevent one additional seizure for every 131 patients treated.
The seizure risk reduction effect of semaglutide cannot be explained solely by decreases in blood glucose or body weight. The contribution of blood glucose reduction (changes in HbA1c) to seizure prevention was analyzed to be only 2.4–6.5%, and the contribution of weight loss (changes in body mass index) was 0.7% or less.
In addition, other GLP-1 receptor agonists did not show a clear seizure-preventive effect comparable to that of semaglutide. The research team suggested that semaglutide’s unique pharmacological properties—its long residence time in the body and partial penetration into the brain—may underlie its preventive effect
Professor Jang said, “This study takes a fresh look at adult-onset seizures from the perspective of brain health in midlife,” adding, “However, because this is an observational study, long-term follow-up studies and randomized clinical trials will be needed to verify the actual preventive effect and its potential for clinical application.”
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