Acute Nutritional Axonal Neuropathy in the Setting of Semaglutide-Associated Gastrointestinal Intolerance: A Case Report

Objectives: To report a unique case of severe sensorimotor polyneuropathy due to acute nutritional axonal neuropathy (ANAN) associated with thiamine and other vitamin deficiencies in the setting of semaglutide-related malnutrition, emphasizing early recognition and intervention to prevent permanent neurologic injury. Methods: A 65-year-old woman with type 2 diabetes and obesity presented with profound weakness, cranial nerve deficits, dysphagia, and a 120-pound weight loss after months of semaglutide therapy with persistent nausea and vomiting. Neurologic examination was performed and cerebrospinal fluid analysis and serum vitamin levels were obtained. Electromyography (EMG) demonstrated absent sensory responses and mild motor slowing, consistent with severe sensory-predominant polyneuropathy. Serum levels of thiamine, folate, and vitamin B12 were below normal, and supplementation was administered. Results: Within five days of thiamine, folate, and vitamin B12 supplementation, the patient showed improvement in cognition and bulbar and limb strength. Oral intake improved over one week, and partial functional recovery was achieved. Discussion: This case of ANAN highlights a severe yet potentially reversible neurologic complication of nutritional deficiencies occurring in the setting of GLP-1 receptor agonist–associated gastrointestinal intolerance and malnutrition. Recognizing and addressing nutrient deficiencies in patients with sensorimotor and/or cognitive deficits after persistent gastrointestinal symptoms can improve deficits and prevent long-term or permanent neurologic injury. Practical Implications: Clinicians should maintain a high suspicion for thiamine, folate, vitamin B12, and other nutritional deficiencies in patients on GLP-1 receptor agonists presenting with neuropathy, unexplained weakness, cranial nerve deficits, and/or confusion, as prompt supplementation may mitigate neurologic injury.