Semaglutide, widely used to treat diabetes and obesity, may significantly reduce the risk of adult-onset seizures, according to a new study. Semaglutide is the active ingredient in the GLP-1 (glucagon-like peptide-1) drug Wegovy, often referred to as a “dream weight-loss drug.”
Seoul National University Hospital announced on July 23 that a joint research team led by Prof. Jang Yoon-hyuk of the National Strategic Technology Specialized Research Institute (Department of Neurology), Prof. Lee Soon-tae of the Department of Neurology, Prof. Eun Yong of Columbia University, and Bong Soo-hwan, a doctoral student at the Harvard T.H. Chan School of Public Health, had published the findings.
Adult-onset seizures refer to seizures that first occur after the age of 18. New-onset seizures in middle-aged and older adults are often associated with acquired brain injuries such as stroke, neurodegenerative diseases, and traumatic brain injury, making them an important indicator of brain health.
Once seizures begin, they can cause loss of consciousness and increase the risk of falls, while also limiting a patient’s ability to drive and participate in daily activities, significantly affecting functional outcomes and quality of life. Current treatment focuses on preventing recurrence with anti-seizure medications after seizures occur, but no established therapy exists to prevent seizures from developing in the first place.
Semaglutide, the focus of the study, has already demonstrated protective effects across multiple diseases. The American Diabetes Association recommends it as a first-line treatment for patients with Type 2 diabetes at high cardiovascular risk, and it is also widely used to manage blood sugar and obesity, as well as to treat chronic kidney disease and metabolic dysfunction-associated steatohepatitis (MASH).
The researchers analyzed electronic medical record (EMR) data from the U.S. National Institutes of Health’s (NIH) large-scale “All of Us” health research program.
Among approximately 390,000 participants with available data, the team identified 69,228 patients with Type 2 diabetes. They then analyzed the risk of adult-onset seizures in 18,243 adults aged 18 or older (average age approximately 60–64) who were newly prescribed semaglutide, other glucose-lowering medications, or SGLT2 (sodium-glucose cotransporter-2) inhibitors.
To improve the reliability of comparisons, the researchers used a target trial emulation approach, which aims to replicate the conditions of a randomized clinical trial using observational data. Participants were divided into a semaglutide-versus-other glucose-lowering drug group (10,213 patients) and a semaglutide-versus-SGLT2 inhibitor group (8,605 patients), with adjustments made for age, comorbidities, body mass index (BMI), and other clinical differences.
The analysis found that patients newly treated with semaglutide had a 56% lower risk of developing adult-onset seizures than those receiving other glucose-lowering medications (hazard ratio 0.44). The absolute difference in cumulative four-year seizure risk was 1.78 percentage points.
Compared with SGLT2 inhibitors, semaglutide users had a 52% lower seizure risk (hazard ratio 0.48), with a four-year cumulative risk difference of 1.46 percentage points.
The researchers explained that, when converted into the number needed to treat (NNT), treating 70 patients with semaglutide instead of other glucose-lowering drugs, or 131 patients instead of SGLT2 inhibitors, would prevent one additional case of adult-onset seizures.
Notably, the reduction in seizure risk could not be explained solely by improvements in blood sugar or weight. Mediation analysis found that changes in glycated hemoglobin (HbA1c) accounted for only 2.4% to 6.5% of the effect, depending on the comparison group, while BMI changes explained just 0% to 0.7%.
The same preventive effect was not clearly observed with other GLP-1 medications. The researchers suggested this may be due to semaglutide’s unique pharmacological properties, including its longer duration in the body and ability to partially cross into the brain.
The study is significant because it suggests, using large population-based data, that a metabolic disease treatment could help protect brain health and prevent neurological disorders in a field where preventive strategies remain limited.
“This study reframes adult-onset seizures from the perspective of brain health in middle-aged and older adults,” Prof. Jang said. “However, because this was an observational study, further long-term follow-up studies and randomized clinical trials will be needed to confirm its preventive effect and clinical applicability.”
The findings were recently published in Neurology, the official journal of the American Academy of Neurology.