Real-world experience with GLP-1 receptor agonists in adults with epilepsy following a modified atkins diet.

INTRODUCTION: Epilepsy is associated with obesity and metabolic syndrome, reflecting a well-established bidirectional relationship between metabolic health and seizure outcomes. GLP-1 receptor agonists may provide complementary metabolic benefits alongside ketogenic diet therapies; however, evidence regarding their effects on seizure control, safety, and combined use with ketogenic diets in epilepsy remains limited. METHODS: A retrospective chart review was conducted in patients seen at the Johns Hopkins Adult Epilepsy Diet Center between 2010 and 2026 who initiated the modified Atkins diet (MAD) and subsequently started a GLP-1 medication. Clinical, anthropometric, and laboratory data were obtained at various time points to evaluate seizure stability and metabolic trends. RESULTS: Ten patients were included; four remained on the MAD, while six had stopped MAD before starting GLP-1. The median duration on MAD was 3.5 years (IQR 1.5-6.8) and 1.2 years (IQR 0.7-2.1) on GLP-1. On MAD, patients showed improved seizure stability and achieved significant weight loss, from a median 83.3 kg (IQR 77.5-118.7) to 79.9 kg (IQR 67.8-102.1) with a decrease in BMI from 31.1 (IQR 26.8-34.0) to 29.8 (IQR 23.7-31.8) (both p = 0.02), though the majority of patients later regained the weight. After starting GLP-1, patients experienced further weight loss from a median of 82.6 kg (IQR 78.4-112.9) to 74.6 kg (IQR 62.7-94.1) and a decrease in BMI from 30.9 kg/m² (IQR 27.2-34.7) to 25.5 kg/m² (IQR 23.0-31.9) (both p < 0.01). Overall seizure control remained stable, except for two breakthrough seizures. No major adverse effects were reported, and combined MAD and GLP-1 therapy was associated with reduced appetite and carbohydrate cravings. CONCLUSION: GLP-1 receptor agonist therapy was well tolerated in adults with epilepsy and was associated with reduced appetite and food cravings, supporting its potential role as a safe adjunct to improve metabolic health and dietary adherence in patients on MAD.