Two widely used glucagon-like peptide-1 (GLP-1) drugs for weight loss have been associated with a rare but serious neurological disorder that can lead to permanent brain damage or death.
Researchers have identified a potential link between semaglutide (sold as Ozempic, Wegovy, and Rybelsus) and tirzepatide (sold as Mounjaro and Zepbound) and Wernicke encephalopathy (WE), a condition caused by a severe deficiency in vitamin B1, also known as thiamine.
GLP-1 drugs function by slowing digestion, which helps individuals feel fuller for longer. This can lead to reduced appetite and food intake, potentially resulting in inadequate nutrition, including a deficiency in vitamin B1. Thiamine is essential for brain cells to produce energy; insufficient levels can impair their function.
A study examining nearly 200,000 cases identified 15 instances of Wernicke encephalopathy, finding a disproportionate association with GLP-1 medications compared to other drugs. Most of these cases involved semaglutide or tirzepatide.
The study highlighted that many patients diagnosed with WE experienced gastrointestinal issues such as weight loss, vomiting, loss of appetite, or malnutrition – all factors that can contribute to vitamin B1 deficiency.
Wernicke encephalopathy affects the brain regions responsible for memory and balance, causing symptoms like altered mental state, difficulty walking, and uncontrolled eye movements. However, only a small percentage of patients exhibit all three hallmark symptoms, making diagnosis challenging. As many as 80% of cases may go undiagnosed, with some only identified post-mortem.
If detected early, WE is treatable with vitamin B1 supplementation, often administered intravenously. However, untreated, the condition can be fatal in up to 20% of cases, and up to 85% of survivors may suffer permanent brain damage.
While WE is considered a rare adverse event associated with these drugs, researchers urge clinicians to remain vigilant for symptoms, particularly in patients taking semaglutide or tirzepatide, to prevent severe outcomes.
Historically, WE has been most commonly linked to chronic alcoholism due to its impact on vitamin B1 absorption and storage. Other risk factors include bariatric surgery, which can impair nutrient absorption, and severe food restriction seen in conditions like anorexia. A case was also reported in a teenager experiencing cannabinoid hyperemesis syndrome, characterized by repeated vomiting.
Over 10% of American adults currently use GLP-1 medications for weight loss, underscoring the potential public health significance of this observed association.