Semaglutide, an Obesity Drug, May Lower the Risk of Adult-Onset Seizures

[Financial News] A large-scale international joint study has found that semaglutide, a GLP-1 receptor agonist widely used to treat diabetes and obesity, may significantly reduce the risk of adult-onset seizures.
Beyond its effects on blood sugar control and weight loss, the drug may also offer neuroprotective benefits, raising hopes for a new therapeutic option.
The joint research team, led by Professor Jang Yoon-hyuk and Professor Lee Soon-tae of the National Strategy Technology Specialized Research Institute and Department of Neurology at Seoul National University Hospital, Professor Eun Yong of the Department of Internal Medicine at Columbia University in the United States, and Ph.D. candidate Bong Soo-hwan of Harvard University T.H. Chan School of Public Health, said on the 23rd that an analysis of large-scale medical data from the National Institutes of Health (NIH) showed that patients with Type 2 diabetes (T2D) who received semaglutide had a much lower risk of adult-onset seizures than those treated with other glucose-lowering drugs.
The findings were published in the latest issue of Neurology, the official journal of the American Academy of Neurology.
Adult-onset seizures refer to seizures that first occur after the age of 18. In particular, seizures that develop later in middle-aged and older adults are often linked to acquired brain disorders such as stroke, neurodegenerative disease and traumatic brain injury, making them an important indicator of brain health.
Once a seizure occurs, the risk of loss of consciousness and falls rises, and driving and social activities can also be severely restricted. However, current treatment mainly focuses on suppressing recurrence with antiseizure medications after seizures occur, and there are few treatments aimed at preventing seizures themselves.
Using electronic medical records from the NIH's All of Us program, the team identified 69,228 patients with Type 2 diabetes from a pool of about 390,000 people. It then compared seizure risk by drug type among 18,243 adult patients newly prescribed semaglutide, other glucose-lowering drugs and SGLT2 inhibitors.
The analysis used a target trial emulation method, which applies real-world clinical data while recreating conditions similar to a randomized clinical trial. The team adjusted for a range of variables, including age, comorbidities and body mass index (BMI), to isolate the effect of the drugs themselves.
The results were striking. Patients newly treated with semaglutide had about a 56% lower risk of adult-onset seizures than those taking conventional glucose-lowering drugs. The hazard ratio was 0.44, and the actual four-year cumulative seizure risk fell by 1.78 percentage points.
A similar trend was seen in comparison with SGLT2 inhibitors. The semaglutide group had 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.
The team also calculated the findings in terms of the number needed to treat (NNT). If semaglutide were used instead of other glucose-lowering drugs, treating 70 patients would prevent one additional case of adult-onset seizures. When used instead of SGLT2 inhibitors, one seizure could be prevented for every 131 patients treated.
The researchers noted that the results could not be explained simply by lower blood sugar or weight loss.
Mediation analysis showed that the reduction in hemoglobin A1c (HbA1c) accounted for only 2.4% to 6.5% of the seizure-prevention effect, while the impact of BMI reduction was minimal at 0% to 0.7%. In addition, no similarly clear seizure-prevention effect was observed with other GLP-1 receptor agonists.
The team said semaglutide's pharmacological properties may be related to the findings, as the drug remains in the body for a long time and some of it crosses the blood-brain barrier to act directly on the central nervous system.
This suggests that semaglutide may offer neuroprotective benefits beyond its role as a treatment for metabolic disease.
The study is significant because it points to a new preventive approach in the field of adult-onset seizures, where there have been few prevention strategies.
Professor Jang Yoon-hyuk of the Department of Neurology at Seoul National University Hospital said, "This study is meaningful in that it approaches adult-onset seizures from a new perspective, as a brain health issue in middle and older age." He added, "However, since this was an observational study, further verification through long-term follow-up studies and randomized clinical trials is needed to confirm the actual preventive effect."

[email protected] Kang Jung-mo Reporter