Management of Ozempic (Semaglutide) Overdose
Immediate Assessment and Monitoring
In cases of Ozempic overdose, initiate supportive care based on clinical signs and symptoms, with prolonged observation required due to semaglutide's approximately 1-week half-life 1.
Essential Laboratory Studies
Obtain the following labs immediately:
- Blood glucose monitoring - Check for hypoglycemia, which is the primary acute concern, especially if the patient is on concurrent insulin or insulin secretagogues 2, 3
- Comprehensive metabolic panel (CMP) - Assess for acute kidney injury from dehydration secondary to gastrointestinal losses 2, 3
- Hepatic function panel - Monitor for cholestatic liver dysfunction, which has been reported in overdose cases 4
- Lipase and amylase - Screen for acute pancreatitis, a known serious adverse effect of GLP-1 receptor agonists 2, 3
- Electrolytes - Evaluate for imbalances from severe vomiting and diarrhea 3
Clinical Monitoring Parameters
Monitor continuously for:
- Gastrointestinal symptoms - Nausea, vomiting, diarrhea, abdominal pain, and constipation are dose-dependent and the most common manifestations 2, 5, 3
- Cardiovascular status - Heart rate elevation and blood pressure changes 2
- Mental status - Assess for suicidal ideation, as GLP-1 RAs have been associated with this risk 2, 4
- Renal function - Serial monitoring for acute kidney injury, particularly if severe gastrointestinal losses occur 2, 3
Supportive Care Measures
Gastrointestinal Management
- Administer antiemetics for nausea and vomiting 3
- Provide intravenous fluid resuscitation to correct dehydration and electrolyte imbalances from gastrointestinal losses 3
- Monitor for ileus or small bowel obstruction, which can occur with semaglutide 2
Hypoglycemia Management
- Frequent blood glucose monitoring (every 1-2 hours initially) 3
- Administer dextrose if hypoglycemia develops 3
- Reduce or hold concurrent insulin or insulin secretagogues to prevent hypoglycemia 2
Duration of Observation
A prolonged observation period is mandatory - Given semaglutide's half-life of approximately 1 week, symptoms may persist or develop over several days 1. The case literature demonstrates that:
- One patient remained asymptomatic despite daily injections over 7 days, with no issues noted even 5 weeks post-overdose 3
- Another patient developed multiorgan failure 14 days after a 4-fold overdose 4
- A suicide attempt case showed only mild, self-limiting symptoms 5
Special Considerations and Pitfalls
Common Pitfall: Premature Discharge
Do not discharge patients early based on initial presentation alone - The long half-life means delayed complications can occur days after overdose 1, 4. Observation should extend at least 48-72 hours with clear discharge instructions for delayed symptom monitoring.
Gallbladder and Pancreatic Complications
- Obtain right upper quadrant ultrasound if abdominal pain develops, as cholelithiasis and cholecystitis risk is increased 2, 3
- Serial lipase monitoring for at least 48 hours to detect delayed pancreatitis 2, 3
Gastrointestinal Endoscopy Considerations
If the patient requires endoscopy for any reason (such as evaluation of melena or suspected ulcers as seen in one overdose case 4):
- Expect delayed gastric emptying and retained gastric contents despite prolonged fasting 6
- Consider rapid sequence intubation if general anesthesia is required 6
Mental Health Assessment
Screen for suicidal ideation and common mental disorders - The case of intentional overdose with suicidal intent highlights this risk 4. One patient reported feeling dysphoric prior to self-administering a 4-fold overdose 4.
Prognosis and Expected Outcomes
The safety profile of semaglutide overdose appears favorable based on limited case reports:
- Most cases present with mild, self-limiting symptoms 5
- One asymptomatic case involved 7 mg total over 7 days (7-fold weekly dose) 3
- Severe complications (multiorgan failure) are rare but have been reported with 4-fold overdoses 4
No specific antidote exists - Management remains entirely supportive 1, 3.