Among ten adults with epilepsy managed at Johns Hopkins Adult Epilepsy Diet Center, combining GLP-1 receptor agonists with the modified Atkins diet (MAD) produced clinically meaningful weight loss — median body weight dropped from 82.6 kg to 74.6 kg and BMI fell from 30.9 to 25.5 kg/m² (both p < 0.01). Seizure control remained largely stable, with only two breakthrough events documented. Crucially, patients who had regained weight after discontinuing MAD responded well to GLP-1 therapy, and the combination was associated with reduced appetite and carbohydrate cravings — a mechanistically plausible synergy given GLP-1's role in hypothalamic appetite suppression.
The epilepsy-obesity-metabolic syndrome triad is underappreciated in neurology. Antiseizure medications frequently promote weight gain, while ketogenic diets are notoriously difficult to sustain long-term, as this cohort's weight regain confirms. GLP-1 agonists could address adherence failures by biologically dampening carbohydrate cravings that undermine dietary ketosis. The neurological implications extend further — GLP-1 receptors are expressed in the brain, and animal data hint at direct anticonvulsant properties, making this combination mechanistically interesting beyond metabolic effects alone. However, with only ten patients and a retrospective design, causal claims are premature. The absence of a control group, heterogeneous MAD adherence, and short GLP-1 exposure (median 1.2 years) limit conclusions. This is an incremental but genuinely novel signal warranting a prospective trial in this overlooked population.