EpilepsiaOct 20, 2026

How GLP-1 receptor drugs may change seizure risk depending on the situation

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 21, 2026

Abstract

Recent studies show a predominantly neutral to protective association between GLP-1 receptor agonist use and seizure-related diagnoses.

GLP-1 receptor agonists may have diverse effects on neuronal excitability that depend on the specific brain network involved.
Preclinical evidence indicates both anticonvulsant and neuroprotective properties in certain seizure models, while paradoxical pro-seizure effects are noted in genetic models of absence epilepsy.
Population-level analyses suggest lower rates of new epilepsy or seizure outcomes among patients on GLP-1 receptor agonists, but these studies often rely on administrative data and lack detailed seizure characterization.
Factors such as delayed gastric emptying, rapid metabolic changes, and varying pharmacokinetics of GLP-1 receptor agonists could influence individual susceptibility to seizures.
The effects of GLP-1 receptor agonists on seizure dynamics may vary based on epilepsy subtype, network vulnerability, and the timing of treatment.

Simplified

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used in type 2 diabetes mellitus and obesity and are increasingly considered to exert neuroprotective effects. Recent large-scale clinical and real-world studies report a predominantly neutral to protective association between GLP-1 RA use and seizure- or epilepsy-related diagnoses. However, how these agents affect neuronal excitability in patients with established epileptogenic networks remains insufficiently understood. This narrative review critically examines the experimental and clinical evidence from GLP-1 RA effects on neuronal excitability and seizure susceptibility, with a focus on possible discrepancies between population-level outcomes and individual network-level vulnerability. Preclinical studies demonstrate heterogeneous, network-dependent effects of GLP-1 RAs. Although anticonvulsant and neuroprotective properties are observed in chemically induced seizure models, paradoxical pro-seizure effects occur in genetic absence epilepsy models. In contrast, population-level analyses report neutral to reduced rates of incident epilepsy or seizure-related outcomes under GLP-1 RA therapy. However, these findings are based largely on administrative diagnostic codes, lack epileptological phenotyping, and are not designed to capture transient, exposure-dependent alterations in neuronal excitability or short-term seizure dynamics. Additional factors, including delayed gastric emptying affecting anti-seizure medication absorption, rapid metabolic shifts during titration, blood-brain barrier dysfunction, and agent-specific pharmacokinetics, may further modulate individual susceptibility. We propose that GLP-1 RA effects on neuronal excitability are context dependent, shaped by epilepsy subtype, network vulnerability, exposure dynamics, and treatment phase. Targeted prospective studies incorporating clinical phenotyping, therapeutic drug monitoring, and temporal seizure assessment are required to ensure neurological safety in patients with epilepsy.

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How GLP-1 receptor drugs may change seizure risk depending on the situation

Abstract

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