BACKGROUND
Tirzepatide is a once-weekly injectable therapy for type 2 diabetes mellitus and obesity that acts as a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide receptor agonist. This medication is commonly used for weight loss, but gastrointestinal adverse effects are common among patients receiving tirzepatide. Intractable emesis is among several conditions that can lead to thiamine deficiency and subsequent Wernicke’s encephalopathy (involving ophthalmoplegia, ataxia, and confusion). Recent studies have suggested an association between Wernicke’s encephalopathy and GLP-1 receptor agonists; causality has not been established.
CASE REPORT
A 69-year-old man experienced months of intractable emesis after initiation of tirzepatide therapy. His clinical course progressed to a reduced level of consciousness, requiring intubation for airway protection. Brain magnetic resonance imaging (MRI) subsequently revealed findings consistent with Wernicke’s encephalopathy. The patient’s mental status failed to improve despite high-dose intravenous thiamine replacement, and extensive diagnostic evaluation failed to identify an alternative cause of his encephalopathy. The patient ultimately died while receiving hospice care.
CONCLUSIONS
This patient experienced intractable emesis after initiation of tirzepatide therapy and subsequently developed Wernicke’s encephalopathy attributed to thiamine deficiency. His case underscores the importance of close monitoring during treatment initiation to identify severe adverse effects and potentially harmful dietary changes. The patient’s imaging findings demonstrate severe neurological damage that can occur with prolonged Wernicke’s encephalopathy. Prompt diagnosis and treatment with high-dose intravenous thiamine are necessary to prevent progression to irreversible neurological deficits or death. Wernicke’s encephalopathy was diagnosed based on the clinical course and characteristic MRI findings; biochemical thiamine deficiency was not independently confirmed.

Keywords: Fatal Outcome; Tirzepatide; Wernicke Encephalopathy