GLP-1 receptor agonist toxicity

Background

• GLP-1 receptor agonists (e.g., semaglutide) are injectable medication used for diabetes management and weight loss
  • Semaglutide
  • Liraglutide
• Poison control centers have reported increasing inquiries related to possible overdoses

Clinical Features

Similar to side effects normally associated with these medications, but worse:

• Nausea/vomiting
• Constipation
• Epigastric pain
• Headache
• Tachycardia
• Sweating
• Confusion
• Delirium

Differential Diagnosis

Nausea and vomiting

Critical

• ACS/MI
• Boerhaave's
• DKA
• Intracranial hemorrhage
• Ischemic bowel
• Meningitis
• Sepsis

Emergent

• Acute radiation syndrome
• Acute gastric dilation
• Adrenal insufficiency
• Appendicitis
• Bowel obstruction/ileus
• Carbon monoxide poisoning
• Cholecystitis
• CNS tumor
• Electrolyte abnormalities
• Elevated ICP
• Gastric outlet obstruction, gastric volvulus
• Hyperemesis gravidarum
• Medication related
  • Acetaminophen toxicity
  • Aspirin toxicity
  • Digoxin toxicity
  • Theophylline toxicity
  • GLP-1 receptor agonist toxicity
• Pancreatitis
• Peritonitis
• Ruptured viscus
• Testicular torsion/ovarian torsion

Nonemergent

• Acute gastroenteritis
• Biliary colic
• Cannabinoid hyperemesis syndrome
• Chemotherapy
• Cyclic vomiting syndrome
• ETOH
• Gastritis
• Gastroenteritis
• Gastroparesis
• Hepatitis
• Labyrinthitis
• Migraine
• Medication related
  • Disulfiram effect
  • Erythromycin
  • Ibuprofen
  • Ipecac toxicity
• Motion sickness
• Narcotic withdrawal
• Thyroid
• Pregnancy
• Peptic ulcer disease
• Renal colic
• UTI

Evaluation

Workup

• CBC
• Chemistry
• LFTs + lipase

Diagnosis

• Typically a clinical diagnosis (based on history)

Management

• Symptomatic management
  • Anti-nausa medications (e.g., zofran)
• Consider stopping other glucose-lowering (i.e, diabetic) medications

Disposition

• If symptoms can be controlled, patients can normally be discharged
  • Consider discharge with zofran and hold of diabetic medications for ~1 week