We report a case of a 50-year-old man with obesity and chronic alcohol use disorder who developed Korsakoff syndrome in the setting of rapid weight loss temporally associated with tirzepatide therapy, a dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide (GLP-1/GIP) receptor agonist. Within weeks of treatment initiation, he presented with profound memory impairment and anosognosia. Initial brain magnetic resonance imaging (MRI) was unremarkable, but 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) revealed hypometabolism in the mammillary bodies with progressive involvement of the thalamus and brainstem. Despite intravenous thiamine replacement, cognitive deficits persisted. This case raises concern that rapid weight loss and reduced nutritional intake during GLP-1-based therapy may contribute to the development of Wernicke-Korsakoff syndrome in vulnerable individuals, particularly those with chronic alcohol use disorder, and underscores the importance of nutritional assessment and consideration of thiamine supplementation when initiating these treatments.
Crelier et al. (2026) studied this question.
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