GLP-1 receptor agonist toxicity
Background
- GLP-1 receptor agonists are injectable medication used for diabetes management and weight loss
- Poison control centers have reported increasing inquiries related to possible overdoses
GLP-1 Agonist Types
| Drug (Brand) | Class | Dose | Route | Frequency | Key Indications |
|---|---|---|---|---|---|
| Daily Dosing | |||||
| Exenatide (Byetta) | GLP-1 RA (exendin-4 based) | 5-10 mcg | SC | BID | T2DM |
| Lixisenatide (Adlyxin) | GLP-1 RA (exendin-4 based) | 10-20 mcg | SC | Daily | T2DM |
| Liraglutide (Victoza) | GLP-1 RA (human GLP-1 based) | 0.6-1.8 mg | SC | Daily | T2DM, CV risk reduction |
| Liraglutide (Saxenda) | GLP-1 RA (human GLP-1 based) | 3.0 mg | SC | Daily | Obesity/overweight |
| Weekly Dosing | |||||
| Semaglutide (Ozempic) | GLP-1 RA (human GLP-1 based) | 0.25-2 mg | SC | Weekly | T2DM, CV risk reduction, CKD |
| Semaglutide (Wegovy) | GLP-1 RA (human GLP-1 based) | 0.25-2.4 mg | SC | Weekly | Obesity/overweight, CV risk reduction |
| Semaglutide (Rybelsus) | GLP-1 RA (human GLP-1 based) | 3-14 mg | PO | Daily | T2DM |
| Semaglutide (Wegovy Pill) | GLP-1 RA (human GLP-1 based) | 1.5-25 mg | PO | Daily | Obesity/overweight |
| Dulaglutide (Trulicity) | GLP-1 RA (human GLP-1 based) | 0.75-4.5 mg | SC | Weekly | T2DM, CV risk reduction |
| Tirzepatide (Mounjaro) | Dual GLP-1/GIP RA | 2.5-15 mg | SC | Weekly | T2DM |
| Tirzepatide (Zepbound) | Dual GLP-1/GIP RA | 2.5-15 mg | SC | Weekly | Obesity/overweight, OSA |
- Albiglutide (Tanzeum) — discontinued 2017 (commercial reasons, not safety); removed from table
- Exenatide ER (Bydureon BCise) — discontinued 2023; brand Byetta discontinued 2024 (generic exenatide available)
ED-Relevant Considerations
- Delayed gastric emptying — all GLP-1 RAs slow gastric motility; important for:
- Aspiration risk during procedural sedation and intubation (consider NPO status unreliable)
- Altered absorption of co-administered oral medications
- 2023 ASA guidance recommends holding GLP-1 RAs prior to elective procedures requiring anesthesia
- Pancreatitis — rare but serious; discontinue if pancreatitis confirmed
- Hypoglycemia — low risk as monotherapy; increased risk when combined with sulfonylurea or insulin
- Nausea/vomiting — most common adverse effect; dose-dependent, typically improves with time
- Injection site reactions — generally mild
- Cholelithiasis/cholecystitis — increased incidence reported
- Contraindicated in personal/family history of medullary thyroid carcinoma or MEN type 2
Clinical Features
Similar to side effects normally associated with these medications, but worse:
Differential Diagnosis
Nausea and vomiting
Critical
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
- 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
- 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