Semaglutide-induced Wernicke encephalopathy: a comprehensive analysis.
Level 4 - case-series / case-control
Case report combined with a case series and pharmacovigilance disproportionality analysis
PubMed 40908328 · doi:10.1038/s41430-025-01653-7
What was done
The authors presented an index case of a 49-year-old woman treated with semaglutide for obesity who developed Wernicke encephalopathy. They also aggregated 18 additional cases identified from the published literature and the World Health Organization global safety database (VigiBase) and performed a disproportionality analysis evaluating reports of Wernicke encephalopathy with semaglutide, tirzepatide, and the broader GLP-1 receptor agonist class.
What was found
A total of 19 cases of Wernicke encephalopathy were evaluated (1 index case plus 18 from literature/VigiBase). Symptoms of nausea, vomiting, or reduced food intake occurred in 68% of cases, with documented weight loss ranging from -3.5 to -13.3 kg per month over 3 to 6 months. Disproportionality analysis showed that Wernicke encephalopathy was disproportionately reported for semaglutide, tirzepatide, and the overall GLP-1 receptor agonist class; specific numerical disproportionality scores or confidence intervals were not provided in the abstract.
Why it matters
These findings identify a clinically important safety signal where severe gastrointestinal adverse effects and rapid weight loss from GLP-1 receptor agonists may precipitate acute thiamine deficiency and Wernicke encephalopathy.
Limits
The evidence is limited to spontaneous adverse event reporting and a small case series (n = 19), which cannot determine true incidence, establish direct causality, or control for confounding. The abstract omits precise statistical metrics for the disproportionality analysis and details on patient outcomes or thiamine repletion courses.
Cited by
- supports Severe neurological presentations linked to high-dose GLP-1 use are caused by acute thiamine (vitamin B1) deficiency leading to Wernicke's encephalopathy.