Massive Accidental Semaglutide Overdose Induces Prolonged Generalized Dysesthesia Without Gastrointestinal Symptoms
Background
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) like semaglutide are widely used for obesity and metabolic diseases, with well-established gastrointestinal adverse effects. While hypoglycemia and pancreatitis are uncommon, potential dose-related neurologic effects remain incompletely characterized. Pharmacovigilance data hint at a broad spectrum of neurologic complaints, and clinical trials (e.g., OASIS-1) suggest a dose-related signal for dysesthesia. However, data on acute supratherapeutic parenteral exposure, particularly concerning neurologic manifestations, is limited, creating a critical knowledge gap this case addresses.
Study Design
This case report details a 50-year-old man with obesity (BMI 36.7 kg/m2) who had been receiving semaglutide 2.4 mg weekly subcutaneously for 8 months without significant side effects. During the first use of a new pen, he accidentally administered his prescribed 2.4 mg dose, but observing remaining liquid, injected again, resulting in a total estimated dose of 16 mg (approximately 8 times his weekly maintenance dose). The patient was then monitored for adverse effects, with particular attention to neurologic and gastrointestinal symptoms, and blood glucose levels.
Results
Following the accidental 16 mg semaglutide overdose, the patient developed isolated generalized dysesthesia, characterized by 'pins and needles,' 'burning,' and 'itching' sensations. The symptoms began approximately 12 hours post-injection, peaked around 24 hours, and persisted for 7 days, gradually resolving over a total period of 14 days. Crucially, the patient reported no gastrointestinal adverse effects, such as nausea, vomiting, or diarrhea, which are typically associated with GLP-1 RA initiation or dose escalation. Blood glucose levels remained within the normal range throughout the observation period, indicating no significant hypoglycemic event. This presentation highlights a distinct neurologic toxicity profile at high doses.
The accidental administration of 16 mg semaglutide led to prolonged, generalized dysesthesia lasting 14 days, without any concurrent gastrointestinal symptoms or hypoglycemia.
Key Findings
- Accidental 16 mg semaglutide overdose occurred (8x weekly maintenance dose).
- Generalized dysesthesia began 12 hours post-injection, peaking at 24 hours.
- Dysesthesia persisted for 7 days, with full resolution over 14 days.
- No gastrointestinal adverse effects (nausea, vomiting, diarrhea) were observed.
- Blood glucose levels remained normal throughout the event.
Why It Matters
This case report significantly expands the known adverse effect profile of semaglutide, particularly at supratherapeutic doses. Emergency physicians should consider isolated neurologic symptoms like prolonged dysesthesia in cases of semaglutide overdose, even in the absence of typical gastrointestinal distress. This finding suggests a direct neurologic effect of high-dose semaglutide, independent of its well-known gut-mediated actions. For peptide users and clinicians, this underscores the importance of meticulous dose verification and patient education on proper injection techniques to prevent accidental overdoses. It also prompts further research into the specific GLP-1R mechanisms in the central nervous system that might mediate such sensory disturbances.
semaglutide
overdose
dysesthesia
neurologic-adverse-event
case-report
glp-1-agonist