Management of Tirzepatide-Associated Pancreatitis

If pancreatitis is suspected in a patient taking tirzepatide, discontinue the medication immediately and initiate appropriate management. 1, 2

Clinical Presentation and Diagnosis

Patients with tirzepatide-associated pancreatitis typically present with persistent severe abdominal pain (sometimes radiating to the back), which may be accompanied by nausea and vomiting 2
Laboratory evaluation should include serum lipase and amylase levels, which are typically elevated in acute pancreatitis 1
Imaging studies such as abdominal CT or MRI should be performed to confirm the diagnosis and assess severity 1
Rule out other common causes of pancreatitis (gallstones, alcohol, hypertriglyceridemia) 3

Discontinue tirzepatide immediately upon suspicion of pancreatitis 1, 2
Provide supportive care:
- Nothing by mouth (NPO) initially to rest the pancreas 1
- Intravenous fluid resuscitation to maintain adequate hydration 1
- Pain management with appropriate analgesics 1
- Monitor for signs of organ dysfunction or complications 1

Monitor vital signs continuously in a high dependency care unit if organ dysfunction occurs 1
Watch for development of:
- Respiratory complications (pleural effusions, acute respiratory distress syndrome) 4
- Renal complications (acute kidney injury due to dehydration) 2
- Local complications (pancreatic necrosis, pseudocyst formation) 5
- Systemic complications (shock, multi-organ failure) 5

Enteral nutrition is recommended over total parenteral nutrition (TPN) to prevent gut failure and infectious complications 1
Both gastric and jejunal feeding can be delivered safely once the patient's condition stabilizes 1
If enteral route is not completely tolerated, partial parenteral nutrition can be considered to meet caloric and protein requirements 1

Tirzepatide should not be restarted in patients who have experienced pancreatitis 1, 2
Consider alternative medications for glycemic control or weight management that are not associated with pancreatitis risk 1
For patients with diabetes, other antidiabetic medications such as metformin, SGLT-2 inhibitors, or insulin may be considered based on individual factors 1
For patients using tirzepatide for weight management, alternative weight loss medications such as phentermine-topiramate or naltrexone-bupropion could be considered 1

Tirzepatide has not been studied in patients with a prior history of pancreatitis, and it is unknown if these patients are at higher risk 2
The incidence of acute pancreatitis with tirzepatide is reported to be rare (≤1%) in clinical trials 6
However, recent case reports suggest that severe and even fatal necrotizing pancreatitis can occur 4, 5
Patients should be educated about the symptoms of pancreatitis and advised to seek immediate medical attention if these develop 2

Patients with gallstones may have an increased risk of tirzepatide-associated pancreatitis 3
Patients transitioning between different GLP-1 receptor agonists (e.g., from semaglutide to tirzepatide) may have a potentially increased risk of adverse effects including pancreatitis 4
Careful dose titration when initiating tirzepatide may help reduce the risk of adverse effects 4

Delaying discontinuation of tirzepatide when pancreatitis is suspected 2
Failing to provide adequate fluid resuscitation, which can worsen outcomes 1
Premature reintroduction of oral feeding before clinical improvement 1
Restarting tirzepatide or another GLP-1/GIP receptor agonist after a patient has experienced pancreatitis 1, 2
Overlooking the possibility of necrotizing pancreatitis, which can be fatal 5