Glucose-lowering drugs may reduce risk of developing epilepsy

A preliminary study of people with diabetes suggests that use of glucose-lowering GLP-1 drugs may be linked to a lower risk of developing epilepsy. The study was published on December 10, 2025, in Neurology^®, the medical journal of the American Academy of Neurology. Glucagon-like peptide-1 receptor agonists, or GLP-1 drugs, have been used for diabetes and weight loss.

The study does not prove that GLP-1 drugs lower the risk of developing epilepsy; it only shows an association.

"Additional randomized, controlled trials that follow people over time are needed to confirm these findings, but these results are promising, since people with diabetes are at increased risk for developing epilepsy later in life," said study author Edy Kornelius, MD, PhD, of Chung Shan Medical University in Taichung, Taiwan. "Epilepsy can have many physical, psychological and social consequences, and many people do not respond to the current medications, so finding ways to reduce this risk is critical."

For the study, researchers examined a U.S. health database for adults with type 2 diabetes who started taking either a GLP-1 drug or another type of drug called dipeptidyl peptidase-4 inhibitor (known as DPP-4 inhibitors or gliptins). None of the people had a previous diagnosis of epilepsy or seizure. The GLP-1 drugs included in the study were dulaglutide, liraglutide and semaglutide.

The 452,766 participants had an average age of 61. Half took the GLP-1 drugs and half took the DPP-4 inhibitors. They were followed for at least five years. During that time, 1,670 people taking the GLP-1 drugs developed epilepsy, or 2.35%, compared to 1,886 people taking the DPP-4 inhibitors, or 2.41%.

Once researchers adjusted for other factors that could affect the risk of epilepsy, such as age, high blood pressure and cardiovascular disease, they found that people taking the GLP-1 drugs were 16% less likely to develop epilepsy than people taking the DPP-4 inhibitors.

When researchers looked at the individual drugs, they found that the association with a lower risk of epilepsy was strongest with the drug semaglutide. 

"More research is needed, but these findings support the theory that GLP-1 drugs may have neurological benefits beyond controlling blood sugar," Kornelius said. "It should be noted that these findings do not imply that DPP-4 inhibitors are harmful in any way or that GLP-1 drugs are definitely beneficial for brain health."

Kornelius said that tirzepatide, a dual GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptor agonist, was not included in the study, as it was introduced after the study period had started. Therefore, the findings may not apply to tirzepatide.

In addition to the limitations of the retrospective, observational design of the study, the study has other limitations. Researchers did not have information on other factors that could affect the risk of epilepsy, such as family history, genetic susceptibility or alcohol use. It's also possible that other factors such as cost, insurance restrictions or how severe the person's diabetes was could affect which drug they were prescribed, which could lead to differences between the two groups.

The study was supported by Chung Shan Medical University Hospital.