Although GLP-1 receptors analogues (RAs) benefits-risks profile has been largely documented in diabetes, higher dosages recently approved in obesity still require further assessment. We describe here the case of a 49-year-old female patient treated with semaglutide for obesity, who presented with Wernicke encephalopathy in a context of iterative vomiting and reduced food intake. Eighteen other cases of Wernicke encephalopathy were reported in literature and in the WHO global safety database (VigiBase). A context of nausea/vomiting or reduced food intake is described in 68% of cases, with weight loss ranging from -3.5 to -13.3 kg/month over 3 to 6 months. Disproportionality analysis in VigiBase showed that Wernicke encephalopathy was disproportionately reported with semaglutide, tirzepatide and the whole GLP-1RAs group. Altogether, this comprehensive analysis supports a safety signal regarding the risk of Wernicke encephalopathy with GLP-1RAs, which requires a prompt assessment, accounting for the growing use of these drugs.