Endocrinologists are being urged to remain alert for thiamine deficiency in patients receiving GLP-1RAs for obesity, in light of a recent case series linking semaglutide to a “rare but potentially devastating” neurological disorder.
Writing in the journal Obesity [link here], the Dutch researchers said while Wernicke’s encephalopathy had not been identified as a complication of semaglutide in large-scale clinical trials, case reports highlighting an association had emerged among patients treated for obesity in clinical practice.
They advised persistent gastrointestinal intolerance such as nausea, vomiting or reduced nutritional intake in such patients should prompt early consideration of thiamine deficiency so patients could be treated before neurological deterioration.
Their case series included six reports with “sufficient information” on the clinical diagnosis of Wernicke’s encephalopathy following semaglutide use (Ozempic or Wegovy) for obesity following a systematic review of the published literature.
Patients were mostly female (67%) and typically middle age (mean age 47, range 37–74 years), had been receiving semaglutide for about 5 months on average (range: 2.5–12 months), and all but one had comorbid somatic and/or psychiatric disorders, which had likely accelerated their thiamine deficiency.
These disorders included anxiety, COPD, diabetes, hyperlipidemia, hypertension, major depressive disorder, polysubstance abuse, ischemic stroke, coronary artery disease, hypothyroidism, Cushing’s syndrome and chronic kidney disease.
Before Wernicke’s encephalopathy onset, patients experienced prolonged gastrointestinal symptoms such as vomiting and constipation, loss of appetite, weakness, and substantial weight loss, noted the researchers from the Helmholtz Institute at Utrecht University in the Netherlands.
Patients also showed signs of the classic triad of symptoms that characterises Wernicke’s encephalopathy: ataxia, ocular abnormalities and mental status change (confusion, delirium or memory loss).
- Mental status change occurred in five cases
- Signs of nystagmus of the eyes in five cases
- Signs of ataxic gait disturbance in four cases
- The full triad of symptoms in three cases
MRI findings were consistent with thiamine deficiency, the researchers said.
Most patients received suboptimal thiamine dosing as treatment, resulting in poor outcomes, including the death of one patient and prolonged memory issues related to chronic Korsakoff syndrome in four patients, the researchers noted.
Only one patient of the six made a full recovery.
The researchers stressed that immediate high-dose parenteral thiamine administration was essential when neurological symptoms emerged to prevent irreversible neurological sequelae and should happen regardless of laboratory results, as serum thiamine levels weren’t sensitive nor specific for deficiency.
They also noted GLP-1RAs other than semaglutide had been linked to the neurological disorder in recent pharmacovigilance data, including tirzepatide.
“As the use of GLP-1RAs continues to expand, clinicians should maintain a high index of suspicion for Wernicke’s encephalopathy in symptomatic patients and initiate prompt parenteral thiamine therapy when indicated,” they said.
“Prophylactic supplementation may be warranted in high-risk individuals, though prospective studies are needed to evaluate its effectiveness.”
They suggested there should also be prospective research to clarify incidence, identify high-risk populations, and develop evidence-based prevention strategies.