GLP-1 drugs linked to reduced risk of epilepsy

A retrospective analysis of data from adults treated for type-2 diabetes indicates that glucose-lowering GLP-1 drugs could be linked to a lower risk of epilepsy.

The findings appeared on December 10, 2025, in Neurology.

“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.”

The researchers extracted and evaluated data from a U.S. health database for adults with type 2 diabetes who were treated with either a GLP-1 drug or another type of drug called dipeptidyl peptidase-4 inhibitor (known as DPP-4 inhibitors or gliptins).

The GLP-1 drugs tracked in the new analysis were dulaglutide, liraglutide and semaglutide.

The study included data from 452,766 subjects with 226,383 in each cohort (GLP-1 or DPP-4). Mean age was 60.5 years and 47.1% were female.

The researchers did not enroll any subjects with a history of epilepsy or seizure.

All were tracked for at least 5 years.

During follow-up, 1,670 subjects in the GLP-1 cohort and 1,886 in the DPP-4 cohort developed epilepsy, or 2.35% vs 2.41%.

Treatment with GLP-1 was associated with a significantly lower risk of epilepsy (16%) compared to DPP-4 treatment.

Semaglutide showed the strongest association with reduced epilepsy risk among the GLP-1 drugs evaluated in the study.

The authors concluded, “GLP- 1RA therapy was associated with a significantly lower epilepsy risk compared with DPP-4i use in adults with T2DM [type 2 diabetes]. These results support the hypothesis that GLP-1 RAs may exert neurologic benefits beyond glycemic control.”

Kornelius added. “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 also noted that tirzepatide, a dual GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptor agonist, was not evaluated since it was approved after the beginning of the study period.