GLP-1 receptor agonists in people with epilepsy: A scoping review of clinical data, safety, and therapeutic...

People with epilepsy (PWE) carry a disproportionate burden of type 2 diabetes mellitus, obesity, and cardiovascular disease, conditions for which glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed. As the use of these agents expands, neurologists are more frequently involved in the care of patients receiving GLP-1-based therapies. We reviewed current evidence regarding the neurologic safety, pharmacokinetic considerations, and potential clinical implications of GLP-1 RAs in PWE.

We conducted a scoping review following PRISMA-ScR principles of preclinical studies, observational cohorts, meta-analyses, and pharmacokinetic reports evaluating GLP-1 RA use in relation to seizures, epilepsy outcomes, antiseizure medication interactions (ASMs), and safety.

Preclinical studies consistently suggest antiseizure and neuroprotective effects mediated through modulation of neuroinflammation, oxidative stress, and neuronal survival pathways. In human populations, large observational cohorts and meta-analyses have associated GLP-1 RA use with lower risks of incident seizures, reduced seizure recurrence, and fewer severe outcomes, including status epilepticus and hospitalization, with relative risk reductions ranging from approximately 10% to 57% across studies. GLP-1 RAs delay gastric emptying and may alter the timing of ASMs absorption; however, overall drug exposure appears largely unchanged in most cases. Available clinical and pharmacovigilance data do not indicate increased risks of seizure worsening or major neuropsychiatric adverse events.

Current evidence suggests that GLP-1 RAs are generally safe and clinically relevant in appropriately selected PWE, with potential benefits extending beyond metabolic control. Because available human data remain largely observational, prospective epilepsy-specific studies are needed to clarify their long-term neurologic impact.