Tirzepatide-induced rapid weight loss linked to Korsakoff syndrome in a patient with chronic alcohol use disorder
Background
Korsakoff syndrome is a severe neurological disorder, often a sequela of Wernicke encephalopathy, primarily caused by thiamine (vitamin B1) deficiency. It manifests as profound memory impairment and confabulation. Individuals with chronic alcohol use disorder are particularly vulnerable due to poor nutrition and impaired thiamine absorption. While GLP-1/GIP receptor agonists like tirzepatide are highly effective for obesity and type 2 diabetes, their mechanism of action often leads to significant appetite suppression and rapid weight loss, which can exacerbate nutritional deficiencies in predisposed individuals. This case highlights a potential, albeit rare, adverse event.
Study Design
This is a case report detailing a 50-year-old man with obesity and chronic alcohol use disorder. He was initiated on tirzepatide therapy for weight management. The primary diagnostic tools included brain magnetic resonance imaging (MRI) and longitudinal 18F-FDG PET scans. The patient's clinical presentation, including profound memory impairment and anosognosia, was monitored. Intervention included intravenous thiamine replacement after diagnosis of Korsakoff syndrome.
Results
Within weeks of tirzepatide initiation, the 50-year-old man presented with profound memory impairment and anosognosia. Initial brain MRI was unremarkable.
18F-FDG PETimaging revealed significant hypometabolism in the mammillary bodies, which progressively extended to involve the thalamus and brainstem. ThesePETfindings are characteristic of Wernicke-Korsakoff syndrome, indicating severe neuronal dysfunction in critical memory and consciousness circuits. Despite prompt intravenous thiamine replacement therapy, the patient's severe cognitive deficits, including memory impairment, persisted. This temporal association strongly suggests that the rapid weight loss and reduced nutritional intake induced by tirzepatide therapy likely contributed to the development or exacerbation of thiamine deficiency in this vulnerable individual with chronic alcohol use disorder.
Key Findings
- A 50-year-old man with obesity and chronic alcohol use disorder developed Korsakoff syndrome after tirzepatide initiation.
- Profound memory impairment and anosognosia emerged within weeks of therapy.
18F-FDG PETshowed hypometabolism in mammillary bodies, progressing to thalamus and brainstem.- Cognitive deficits persisted despite intravenous thiamine replacement.
- Rapid weight loss and reduced nutritional intake with tirzepatide may contribute to Wernicke-Korsakoff syndrome in vulnerable individuals.
Why It Matters
Clinicians should consider thiamine supplementation and thorough nutritional assessment for vulnerable patients, especially those with chronic alcohol use disorder, when initiating GLP-1-based therapies like tirzepatide. This case underscores a critical, albeit rare, safety consideration for tirzepatide and other GLP-1/GIP agonists. While these drugs are highly effective for obesity and diabetes, their potent appetite-suppressing effects can lead to rapid weight loss and reduced overall nutritional intake. For individuals with pre-existing risk factors for thiamine deficiency, such as chronic alcohol use disorder, this can precipitate severe neurological complications like Wernicke-Korsakoff syndrome. This finding suggests a need for enhanced vigilance and proactive nutritional support in specific patient populations to prevent such adverse outcomes.
tirzepatide
korsakoff syndrome
wernicke-korsakoff
alcohol use disorder
obesity
thiamine deficiency