Wernicke encephalopathy emerges as a possible safety signal in patients on GLP-1 receptor agonists, analysis suggests
Presenter: Manar Kadhem, MD, Mansoura University, Mansoura, Egypt
Wernicke encephalopathy in patients treated with glucagon-like peptide-1 receptor agonists: a comprehensive systematic review. Presented April 23, 2026.
Glucagon-like peptide-1 (GLP-1) receptor agonists prescribed for obesity and type 2 diabetes may in rare cases be causing Wernicke encephalopathy, a systematic review and pharmacovigilance analysis presented at AACE 2026 suggest.
The investigation paired three published clinical reports with 18 cases drawn from VigiBase, the World Health Organization's global pharmacovigilance database, and identified a consistent metabolic pattern preceding diagnosis, including pronounced appetite suppression, persistent vomiting, and rapid weight loss, according to study author Manar Kadhem, MD.
Wernicke encephalopathy is classically tied to alcohol use disorder and bariatric surgery, and no unified guidance currently exists for monitoring nutritional deficiencies during rapid weight loss on GLP-1 receptor agonists, the author noted.
“We observed a connection when reviewing global VigiBase data, which showed a noticeably disproportionate reporting of Wernicke encephalopathy for both semaglutide and tirzepatide,” Dr. Kadhem said. “We noticed that patients weren't just losing weight; they were also experiencing severe gastroparesis and persistent vomiting.”
Findings in literature and Vigibase
Searches across PubMed, Google Scholar, and the Cochrane Library through January 2026 returned 209 records. Eligible reports involved adults aged 18 years or older on a GLP-1 receptor agonist who developed Wernicke encephalopathy that was confirmed either clinically or by neuroimaging.
Cases tied to alcohol, bariatric surgery, or pregnancy were excluded. A total of three published clinical reports cleared the threshold.
Across 18 VigiBase reports, the reporting odds ratio was 10.2 (95% confidence interval 5.8 to 17.9) for semaglutide and 11.4 (95% confidence interval 2.8 to 45.8) for tirzepatide. Heterogeneity testing was nonsignificant (I² = 0%; P = .885), pointing to a class-wide rather than agent-specific phenomenon.
Case findings
Median time to onset was 3 to 6 months after the patient began GLP-1 receptor agonist therapy or moved up to a higher dose. The investigators identified what they called a “triple-hit” pathophysiology preceding diagnosis, including iatrogenic gastroparesis; persistent vomiting, which was documented in 100% of cases; and rapid weight loss velocities of 3.5 to 13.3 kg per month, including one patient who lost 30 kg in 12 weeks.
Patients exhibited the classic Wernicke triad of disorientation, ataxia, and ophthalmoplegia or nystagmus, according to Dr. Kadhem. Brain MRI uniformly revealed bilateral, symmetric T2/FLAIR signal abnormalities in the medial thalami and periaqueductal gray matter. Serum thiamine was low in every patient tested.
High-dose intravenous thiamine, given at 500 to 1,500 mg per day, quickly reversed the physical signs of the syndrome. Even so, approximately 20% patients were discharged with cognitive or memory deficits, according to Dr. Kadhem.
Clinical challenges
Based on these findings, Dr. Kadhem said bariatric nutritional monitoring standards should be extended to high-dose GLP-1 receptor agonist therapy, with a high index of suspicion in any patient experiencing more than 2 weeks of vomiting or altered mental status.
“Don't wait for MRI or lab results if you notice neurological symptoms in a patient experiencing severe GI side effects,” Dr. Kadhem said in an interview. “Administer IV thiamine immediately, as any delay could result in serious complications.”
Recognition of Wernicke encephalopathy may be hampered by the so-called obesity paradox, or the assumption that patients with a high body mass index cannot be malnourished, Dr. Kadhem added.
Disclosures
Manar Kadhem, MD, reported that no external funding was received for this study.
References
Kadhem M. Wernicke encephalopathy in patients treated with glucagon-like peptide-1 receptor agonists: a comprehensive systematic review. Endocr Pract 2026; 32(suppl). https://doi.org/10.1016/j.eprac.2026.03.059