TOPLINE:

Initiation of GLP-1s was associated with an 18% lower risk for seizure recurrence and a 65% and 60% lower risk for hospitalization and mortality, respectively, than initiation of other glucose-lowering medications in adults with both epilepsy and diabetes, a new retrospective cohort study showed.

METHODOLOGY:

• Researchers conducted a retrospective, multinational, propensity score-matched cohort study using electronic health record data from 2003 to 2025 for more than 8000 matched pairs (mean age, 53 years) with type 2 diabetes and at least three diagnoses of epilepsy or recurrent seizures.
• Patients were categorized into the GLP-1 group if they had initiated use of exenatide, liraglutide, dulaglutide, lixisenatide, semaglutide, or tirzepatide (68% women) or the comparator group if they started one of the following alternative glucose-lowering medications: SGLT2 inhibitor, DPP‑4 inhibitor, sulfonylurea, or insulin (69% women).
• The primary outcome was seizure recurrence identified by International Classification of Diseases, 10th Revision, codes. Secondary outcomes were hospitalization, all-cause mortality, status epilepticus, and ICU admission.
• The median follow-up durations for the GLP-1 and comparator groups were 514 days and 415 days, respectively.

TAKEAWAY:

• Participants in the GLP-1 group had a lower risk for seizure recurrence than those in the comparator group (hazard ratio [HR], 0.82; 95% CI, 0.78-0.86), as well as a longer median time to recurrence (1327 vs 891 days, respectively).
• The GLP-1 group also had a greater reduced risk for hospitalization (HR, 0.35; 95% CI, 0.29-0.43), all-cause mortality (HR, 0.40; 95% CI, 0.35-0.46), and status epilepticus occurrence (HR, 0.75; 95% CI, 0.62-0.91).
• Although there was a lower trend for ICU admissions in the GLP-1 group than that in the comparator group (2.2% vs 2.5%; HR, 0.82; 95% CI, 0.67-1.00), the between-group differences were not significant.
• Sensitivity analyses restricted to epilepsy-specific codes confirmed a consistent association between GLP-1 use and reduced seizure recurrence (HR, 0.69), which was independent of the risk for hypoglycemia associated with the comparator therapies.

IN PRACTICE:

The results “support potential neuroprotective roles of GLP-1 signaling,” the investigators wrote.

However, these “hypothesis-generating findings warrant confirmation in prospective studies before translation into clinical practice,” they added. 

SOURCE:

The study was led by Majd A. AbuAlrob, Neuroscience Institute, Hamad Medical Corporation, Doha, Qatar. It was published online on November 18 in Epilepsia.

LIMITATIONS: 

The study was limited by its observational design, which prevented the establishment of causal relationships. Data on key indicators of epilepsy severity, medication adherence, and lifestyle factors were not consistently available in the dataset, and the use of diagnosis codes introduced a potential risk for misclassification. The relatively short median follow‑up durations limited conclusions about long‑term outcomes. Selection bias existed if GLP‑1 receptor agonists were preferentially prescribed to patients with better adherence or more favorable health profiles. Site‑level variations in coding practices or incomplete health data may have introduced further uncertainty.

DISCLOSURES:

The investigators reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.