Glucagon-like peptide-1 receptor agonists and...

Glucagon-like peptide-1 receptor agonists and Wernicke encephalopathy: A pharmacovigilance study and literature review

Abstract

BACKGROUND & AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revolutionized the treatment of type 2 diabetes mellitus and obesity in recent years. While gastrointestinal adverse events are common, their association with nutritional deficiencies, including thiamine, has not been comprehensively investigated. This study aimed to evaluate whether treatment with GLP-1 RAs is associated with the occurrence of Wernicke encephalopathy (WE). METHODS: We conducted a pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) and a narrative literature review. Disproportionality analysis assessed WE reporting following GLP-1 RA treatment using the reporting odds ratio (ROR) and the lower bound of the information component (IC) 95 % credibility interval. RESULTS: We identified 15 cases of GLP-1 RA-associated WE: 13 from FAERS, 1 from published literature, and 1 from our medical center. Most cases occurred with semaglutide (n = 8/15) or tirzepatide (6/15), and were reported in 2023-2024 (14/15). Most patients (13/15) reported gastrointestinal manifestations of either weight loss, vomiting, loss of appetite, or malnutrition. Classic WE symptoms were reported in 11 patients, and the full clinical triad in 2 patients. Long-term neurological sequelae were noted in 7 of 11 patients with follow-up data. Disproportionality analysis showed increased reporting of WE with GLP-1 RAs compared with other medications (ROR = 2.35 [95%CI, 1.38-4.01]; IC₀₂₅ = 0.29). CONCLUSIONS: WE is a potentially rare but severe adverse event of GLP-1 RA treatment, mainly with semaglutide or tirzepatide. As early detection may prevent neurological sequelae, increased clinical awareness is warranted, especially in individuals experiencing severe gastrointestinal symptoms.

Authors

Lev D; Leibowitz A; Lang A; Shlomai G; Twig G; Eden-Friedman Y; Engel T; Cukierman-Yaffe T; Dankner R; Gerstein HC

Journal

Clinical Nutrition, Vol. 57, ,

Publisher

Elsevier

Publication Date

February 1, 2026

DOI

10.1016/j.clnu.2025.106571

ISSN

0261-5614

Associated Experts

Hertzel Chaim Gerstein

Professor, Faculty of Health Sciences

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Glucagon-like peptide-1 receptor agonists and Wernicke encephalopathy: A pharmacovigilance study and literature review

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