What is recommended for a patient with a history (h/o) of gallstones and/or pancreatitis requesting Glucagon-like peptide (GLP) medications?

GLP-1 Medications in Patients with History of Gallstones and/or Pancreatitis

GLP-1 receptor agonists should be used with caution in patients with a history of gallstones and/or pancreatitis, with semaglutide being the preferred option due to its more favorable safety profile in recent studies.

Risk Assessment and Medication Selection

For Patients with History of Gallstones:

• GLP-1 receptor agonists can be prescribed but require careful monitoring as they may increase the risk of gallbladder disease 1
• Both liraglutide and semaglutide carry warnings about potential gallbladder disorders 1, 2
• Monitor for symptoms of cholelithiasis including:
  • Right upper quadrant pain
  • Nausea
  • Vomiting
  • Fever

For Patients with History of Pancreatitis:

• Recent evidence suggests GLP-1 RAs may be safely used in patients with history of pancreatitis 3
• A 2025 TriNetX analysis showed GLP-1 RAs were associated with lower risk of pancreatitis recurrence compared to SGLT2 inhibitors and DPP-4 inhibitors 3
• Another 2025 study found no increased risk of pancreatitis with GLP-1 RAs in comorbidity-free patients with T2DM 4
• However, caution is still warranted as:
  • FDA labeling for liraglutide includes warnings about pancreatitis 5
  • Some older studies suggested increased risk 6
  • A 2025 study indicated dose-dependent pancreatitis risk with GLP-1 agonists 7

Recommended Approach

1. Initial Assessment:

   • Evaluate severity and recency of previous pancreatitis episodes
   • Assess for ongoing gallstone disease
   • Check for other pancreatitis risk factors (alcohol use, hypertriglyceridemia)

2. Medication Selection:

   • First choice: Semaglutide (if appropriate for patient's condition)

     • Can be used without dose adjustment in patients with any degree of renal impairment 2
     • Start with 0.25 mg weekly for 4 weeks, then gradually titrate 2
     • Slower titration may reduce GI side effects

   • Alternative: Liraglutide

     • Titrate dose weekly by 0.6 mg as tolerated 1
     • Start with 0.6 mg daily, maximum dose 3.0 mg daily

3. Monitoring Protocol:

   • Educate patient about symptoms of acute pancreatitis (persistent severe abdominal pain, sometimes radiating to the back, with or without vomiting)
   • Monitor for signs of gallbladder disease
   • If pancreatitis is suspected, promptly discontinue medication and evaluate 5
   • Consider baseline lipase/amylase measurements

Important Precautions

• If patient has active gallstone disease, consider addressing this before starting GLP-1 therapy

• Avoid GLP-1 RAs in patients with:

  • Personal or family history of medullary thyroid carcinoma or MEN2 1, 2
  • Severe hypersensitivity to the drug 2
  • Active acute pancreatitis

• For patients with history of severe or recurrent pancreatitis, consider alternative weight management options such as:

  • Naltrexone ER/bupropion (if no contraindications) 1
  • Metformin (if appropriate for glycemic control) 1

Conclusion

While older studies raised concerns about pancreatitis risk with GLP-1 RAs, more recent evidence suggests they may be used safely in patients with history of pancreatitis. However, careful patient selection, monitoring, and education about warning signs remain essential. The decision should balance the benefits of weight loss and glycemic control against the potential risks.