Is it safe to initiate Ozempic (semaglutide) in patients with a history of cholestasis or pancreatitis?

From the Guidelines

Initiating Ozempic (semaglutide) in patients with a history of cholestasis or pancreatitis requires extreme caution, and it is generally not recommended due to the potential risk of exacerbating these conditions. According to the most recent evidence from 1, semaglutide is contraindicated in patients with a personal or family history of medullary thyroid cancer or MEN2, and it should be used with caution in patients with a history of pancreatitis or cholelithiasis.

The medication's mechanism of action as a GLP-1 analog 1 may increase the risk of acute pancreatitis, and patients should be closely monitored for symptoms like severe abdominal pain, nausea, vomiting, or elevated pancreatic enzymes. For patients with a history of cholestasis, liver function should be monitored closely as semaglutide is primarily metabolized in the liver 1.

Some key points to consider when deciding whether to initiate Ozempic in these patients include:

• The potential benefits of weight loss and improved glycemic control must be carefully weighed against the potential risks of exacerbating pancreatitis or cholestasis.
• Alternative medications should be considered if the risk appears significant.
• If Ozempic is initiated, it is recommended to start with the lowest dose (0.25 mg weekly for 4 weeks) and gradually increase while monitoring for adverse effects 1.
• Regular liver function tests are advisable, particularly in patients with a history of cholestasis.
• Patients should be educated on the signs and symptoms of pancreatitis and cholestasis and instructed to seek immediate medical attention if they experience any severe abdominal pain, nausea, vomiting, or other concerning symptoms.

From the FDA Drug Label

WARNINGS AND PRECAUTIONS • Acute Pancreatitis: Has been observed in patients treated with GLP-1 receptor agonists, including WEGOVY. Discontinue promptly if pancreatitis is suspected. (5. 2). • Acute Gallbladder Disease: Has occurred in clinical trials. If cholelithiasis is suspected, gallbladder studies and clinical follow-up are indicated (5. 3).

Initiation of Ozempic in patients with a history of cholestasis or pancreatitis is not recommended.

• The FDA drug label warns of the risk of acute pancreatitis and acute gallbladder disease with the use of semaglutide, the active ingredient in Ozempic.
• Although the label does not explicitly contraindicate the use of Ozempic in patients with a history of cholestasis or pancreatitis, the risk of recurrence or exacerbation of these conditions cannot be ruled out.
• Given the potential risks, it is prudent to exercise caution and avoid initiating Ozempic in patients with a history of cholestasis or pancreatitis, unless the potential benefits outweigh the risks and the patient is closely monitored 2.

From the Research

Safety of Ozempic (Semaglutide) in Patients with a History of Cholestasis or Pancreatitis

• The safety of semaglutide in patients with a history of cholestasis or pancreatitis is a concern due to potential adverse effects on the pancreas and biliary system 3, 4, 5.
• A study published in Frontiers in Endocrinology found that semaglutide increases the risk of biliary disease (cholelithiasis) 3.
• Another study published in the Journal of Pharmacy Practice reported a case of recurrent pancreatitis in a patient taking semaglutide, suggesting a potential link between the drug and pancreatic inflammation 4.
• However, a large clinical trial (SUSTAIN FORTE) found that semaglutide had a similar safety profile to other GLP-1RAs, with no unexpected safety issues arising 6.
• The prescribing information for oral semaglutide notes that it is not recommended in patients with suspected or confirmed pancreatitis, and it is contraindicated in those with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 7.
• A case report published in Cureus highlighted the potential risk of acute pancreatitis in patients taking semaglutide, emphasizing the need for clinicians to be aware of this potential adverse effect 5.

Initiation of Ozempic in Patients with a History of Cholestasis or Pancreatitis

• Based on the available evidence, it is recommended to exercise caution when initiating semaglutide in patients with a history of cholestasis or pancreatitis 3, 4, 7, 5.
• Patients with a history of pancreatitis should be carefully evaluated and monitored for signs of pancreatic inflammation or other adverse effects 4, 7, 5.
• The benefits and risks of semaglutide should be carefully weighed in patients with a history of cholestasis or pancreatitis, and alternative treatment options should be considered if necessary 3, 7.