GLP-1 Diabetes Medications Linked to Lower Epilepsy Risk

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A large real-world study published in Neurology found that people with Type 2 diabetes taking glucagon-like peptide-1 (GLP-1) receptor agonists had a lower risk of developing epilepsy than those taking dipeptidyl peptidase-4 (DPP-4) inhibitors.

“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 investigator Edy Kornelius, M.D., Ph.D., 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.”

People living with Type 2 diabetes are known to have a higher risk of developing neurological conditions, including epilepsy, especially as they age. While some diabetes medications may have protective effects on the brain, there have been limited real-world data comparing how different treatments influence epilepsy risk.

Investigators explored whether one commonly used class of diabetes drugs — GLP-1 receptor agonists — may reduce the risk of developing epilepsy compared with another class, DPP-4 inhibitors.

What Are GLP-1 Receptor Agonists?

GLP-1 receptor agonists are medications used to treat Type 2 diabetes that help regulate blood sugar by increasing insulin release, slowing digestion and reducing appetite. Drugs in this class include semaglutide, liraglutide and dulaglutide. Previous laboratory studies have suggested these medications may also protect brain cells and reduce inflammation, raising interest in their potential neurological benefits.

How the Study Was Conducted

Investigators analyzed health records from the TriNetX database, which includes real-world medical data from 2015 to 2023. The study included adults with Type 2 diabetes who were newly prescribed either a GLP-1 receptor agonist or a DPP-4 inhibitor.

People with a prior history of epilepsy, seizures or antiseizure medication use were excluded. To ensure fair comparisons, patients in each group were carefully matched based on age, sex, body weight, medical conditions and medications.

Key Findings

More than 450,000 patients were included in the final analysis, with an average age of about 60 years, and about half were female (47%). Over time, fewer people taking GLP-1 receptor agonists developed epilepsy compared with those taking DPP-4 inhibitors (2.35% versus 2.41%, respectively). Overall, GLP-1 receptor agonist use was associated with a 16% lower risk of developing epilepsy. The protective effect was seen as early as one year and continued through five years of follow-up. Among individual medications, semaglutide showed the strongest association with reduced epilepsy risk.

What This Means for Patients

These findings suggest that GLP-1 receptor agonists may offer benefits beyond blood sugar control, potentially helping to lower the risk of epilepsy in people with Type 2 diabetes. While the study does not prove cause and effect, the results were consistent across age and sex groups and remained strong in multiple sensitivity analyses.

Investigators noted that because this was an observational study using medical records, it cannot definitively prove that GLP-1 drugs prevent epilepsy. Other unmeasured factors may still influence risk.

“More research is needed, but these findings support the theory that GLP-1 drugs may have neurological benefits beyond controlling blood sugar,” Kornelius concluded. “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.”