[Sportschosun Reporter Jang Jong-ho] A large population-based study has found that semaglutide, widely used to treat diabetes and obesity, may significantly reduce the risk of adult-onset seizures.
Adult-onset seizures refer to seizures that first occur after age 18. New-onset seizures in middle-aged and older adults are drawing attention as an important indicator of brain health, as they may be linked to acquired brain injury such as stroke, neurodegenerative disease, or traumatic brain injury.
Once a seizure begins, it can lead to loss of consciousness or falls, and it may restrict driving and social activities, greatly affecting a patient's functional prognosis and quality of life. However, current treatment is limited to suppressing recurrence with anti-seizure medication after seizures occur, and there is no fundamental strategy to prevent seizures themselves.
Against this backdrop, a joint research team led by Professor Jang Yoon-hyuk of the Seoul National University Hospital National Strategic Technology Specialized Research Institute and the Department of Neurology, Professor Lee Soon-tae, Professor Eun Yong of Columbia University's Department of Internal Medicine, and Ph.D. candidate Bong Soo-hwan of Harvard University's T.H. Chan School of Public Health announced on the 23rd a study analyzing the association between semaglutide use and the occurrence of adult-onset seizures.
The target of the study, semaglutide, is a treatment that has demonstrated protective effects across multiple diseases. The American Diabetes Association recommends it as a first-line treatment for patients with type 2 diabetes (T2D) at high risk of cardiovascular disease, and it is already widely used not only for blood sugar and obesity management but also for chronic kidney disease and metabolic dysfunction-associated steatohepatitis.
The research team used electronic medical record (EMR) data from the All of Us program, a large health care cohort of the National Institutes of Health (NIH). From about 390,000 people with available data, they selected 69,228 patients with T2D and then analyzed the risk of adult-onset seizures among 18,243 adult patients aged 18 or older, with an average age of about 60 to 64, who had newly been prescribed semaglutide, other glucose-lowering drugs, or SGLT2 inhibitors.
To ensure a precise comparison, the team applied a target trial emulation method that closely mirrors randomized clinical trials using observational data. They divided the patients into a semaglutide-versus-other-glucose-lowering-drugs group (10,213 patients) and a semaglutide-versus-SGLT2 inhibitors group (8,605 patients), then carefully adjusted for clinical differences such as age, comorbidities, and body mass index (BMI) to assess the drug's effect.
The analysis showed that the newly treated semaglutide group had about a 56% lower risk of adult-onset seizures than the group receiving other glucose-lowering drugs, with a hazard ratio of 0.44. The four-year cumulative risk difference, which reflects the actual difference in seizure incidence, was 1.78 percentage points. In the comparison with SGLT2 inhibitors, the semaglutide group also showed about a 52% lower seizure risk, with a hazard ratio of 0.48, and a four-year cumulative risk difference of 1.46 percentage points.
Converted into the clinically used measure of number needed to treat (NNT), this means that treating 70 patients with semaglutide instead of other glucose-lowering drugs, or 131 patients instead of SGLT2 inhibitors, could prevent one additional case of adult-onset seizure.
In particular, the reduction in seizure risk could not be explained solely by improvements in blood sugar or weight. Mediation analysis showed that changes in glycated hemoglobin accounted for only 2.4% to 6.5% of the effect, depending on the comparison group, while changes in body mass index (BMI) accounted for just 0% to 0.7%. The preventive effect was also not clearly observed with other GLP-1 class drugs. The research team suggested that semaglutide's unique pharmacological properties, including its long residence time in the body and partial penetration into the brain, may explain the finding.
This study is significant in that it used large-scale population-based data to suggest that a metabolic disease treatment may contribute to brain health and the prevention of neurological disorders in the field of adult-onset seizures, where preventive strategies are limited.
Professor Jang Yoon-hyuk of the National Strategic Technology Specialized Research Institute and the Department of Neurology said, "This study offers a new perspective on adult-onset seizures as an issue of brain health in middle age." He added, "However, since this is an observational study, long-term follow-up studies and randomized clinical trials will be needed in the future to verify the actual preventive effect and its clinical applicability."
The findings were published in a recent issue of Neurology, the official journal of the American Academy of Neurology.
Jang Jong-ho, bellho@sportschosun.com
This article has been translated by GripLabs Mingo AI.
