Glucagon-like peptide-1 receptor agonists and Wernicke encephalopathy: A pharmacovigilance study and literature review.
Level 4 - case-series / case-control
Pharmacovigilance disproportionality analysis (FAERS) and case series
PubMed 41534460 · doi:10.1016/j.clnu.2025.106571
What was done
The authors conducted a pharmacovigilance disproportionality analysis using the FDA Adverse Event Reporting System (FAERS), along with a literature review and single-center medical records, to evaluate Wernicke encephalopathy (WE) reports linked to GLP-1 receptor agonist (GLP-1 RA) treatment. Disproportionality was measured using reporting odds ratios (ROR) and the lower bound of the 95% credibility interval of the information component (IC025).
What was found
The authors identified 15 cases of GLP-1 RA-associated WE (13 from FAERS, 1 from literature, 1 institutional). Most cases were associated with semaglutide (n = 8/15) or tirzepatide (n = 6/15), and 14 of 15 were reported in 2023–2024. Gastrointestinal manifestations (weight loss, vomiting, loss of appetite, or malnutrition) were present in 13 of 15 patients. Classic WE symptoms were reported in 11 patients and the full clinical triad in 2; 7 of 11 patients with follow-up developed long-term neurological sequelae. Disproportionality analysis showed higher reporting of WE with GLP-1 RAs compared to other drugs (ROR = 2.35 [95% CI, 1.38–4.01]; IC025 = 0.29).
Why it matters
This study highlights Wernicke encephalopathy as a rare but disabling potential consequence of GLP-1 RA-induced gastrointestinal symptoms and malnutrition, underscoring the need for early thiamine monitoring and replacement.
Limits
FAERS data lack exposure denominators, precluding true incidence calculation, and are prone to reporting bias, confounding, and incomplete clinical information. The total number of identified cases was small (n = 15), and causality cannot be definitively proven.
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.