Semaglutide-induced Wernicke encephalopathy: a comprehensive analysis

Area of Science:

• Neuroscience
• Endocrinology
• Pharmacology

Background:

• Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for diabetes management.
• Recent approvals for obesity involve higher dosages, necessitating updated safety evaluations.
• The neurological risks associated with these higher doses require thorough investigation.

Purpose of the Study:

• To assess the potential association between GLP-1 RAs and Wernicke encephalopathy.
• To analyze reported cases and safety database information regarding this adverse event.
• To evaluate the risk signal in the context of increasing GLP-1 RA usage for obesity.

Main Methods:

• Case report of a patient treated with semaglutide for obesity presenting with Wernicke encephalopathy.
• Systematic literature review and analysis of WHO global safety database (VigiBase) for GLP-1 RA-associated Wernicke encephalopathy cases.
• Disproportionality analysis of adverse event reporting in VigiBase.

Main Results:

• A case of Wernicke encephalopathy was observed in a patient on semaglutide for obesity, associated with vomiting and reduced intake.
• Eighteen additional cases were identified in literature and VigiBase.
• Nausea, vomiting, or reduced food intake were reported in 68% of cases, with significant weight loss.
• Disproportionality analysis indicated a higher reporting rate of Wernicke encephalopathy for semaglutide, tirzepatide, and GLP-1 RAs collectively.

Conclusions:

• A potential safety signal for Wernicke encephalopathy exists with GLP-1 RAs, particularly at higher doses used for obesity.
• The association with gastrointestinal side effects like vomiting and reduced intake is notable.
• Further prompt assessment and clinical vigilance are recommended due to the expanding use of these agents.