What is the risk of pancreatitis with Wegovy (semaglutide)?

From the Guidelines

Wegovy (semaglutide) carries a small but real risk of pancreatitis, and patients should be aware of warning signs including severe abdominal pain that may radiate to the back, sometimes accompanied by vomiting. The risk of pancreatitis associated with Wegovy is a class effect of GLP-1 receptor agonists, and the mechanism likely involves changes in pancreatic enzyme secretion and possibly direct effects on pancreatic tissue 1. Patients with a history of pancreatitis may be at higher risk and should discuss this with their healthcare provider before starting treatment 1. If pancreatitis is suspected, Wegovy should be discontinued immediately and medical attention sought 1. Regular monitoring by healthcare providers is important, especially during the initial months of treatment 1. Despite this risk, for most patients without a history of pancreatic disease, the benefits of Wegovy for weight management typically outweigh this relatively rare adverse effect 1. Some key points to consider when prescribing Wegovy include:

• Use caution in people with kidney disease when initiating or increasing dose due to increased risk of gastrointestinal side effects and potential risk of acute kidney injury from dehydration 1
• Contraindicated for use in combination with monoamine oxidase inhibitors 1
• Do not use if at high risk for glaucoma due to risk of acute angle-closure glaucoma 1
• Risk of suicidal behavior/ideation in people younger than 24 years 1
• Contraindicated in people with unmanaged hypertension and/or hypoglycemia (with concomitant use of insulin or sulfonylurea) 1
• Possible safety concerns and considerations: Rare cases of severe liver injury reported, caution with cardiovascular disease 1

From the FDA Drug Label

In glycemic control trials, acute pancreatitis was confirmed by adjudication in 7 OZEMPIC-treated patients (0.3 cases per 100 patient years) versus 3 in comparator-treated patients (0. 2 cases per 100 patient years). One case of chronic pancreatitis was confirmed in an OZEMPIC-treated patient. After initiation of OZEMPIC, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting) If pancreatitis is suspected, OZEMPIC should be discontinued and appropriate management initiated; if confirmed, OZEMPIC should not be restarted.

The risk of pancreatitis on semaglutide (Wegovy) is present, with a reported incidence of 0.3 cases per 100 patient years in glycemic control trials.

• Key points:
  • Acute pancreatitis was confirmed in 7 OZEMPIC-treated patients.
  • One case of chronic pancreatitis was confirmed in an OZEMPIC-treated patient.
  • Patients should be carefully observed for signs and symptoms of pancreatitis after initiation of OZEMPIC.
  • If pancreatitis is suspected, OZEMPIC should be discontinued and appropriate management initiated. 2

From the Research

Risk of Pancreatitis on Wegovy

• The risk of pancreatitis associated with Wegovy (semaglutide) has been evaluated in several studies 3, 4, 5, 6, 7.
• A meta-analysis of 21 eligible trials of semaglutide, including 34,721 patients, found that semaglutide therapy was not associated with an increased risk of acute pancreatitis (OR 0.7; 95% CI 0.5-1.2, I2 0%) 3.
• A case report presented a patient who developed acute pancreatitis while taking semaglutide, highlighting the need for clinicians to be aware of this potential risk 4.
• A retrospective cohort study using the TriNetX platform found that GLP-1RA users, including those taking semaglutide, experienced significantly lower recurrence rates of acute pancreatitis compared to non-users 5.
• Semaglutide has been shown to have a favorable safety profile, with mostly mild-to-moderate and transient gastrointestinal disturbances, and an increased risk of biliary disease (cholelithiasis) 7.
• The overall risk/benefit profile of semaglutide is considered favorable for patients with type 2 diabetes, with beneficial metabolic and cardiovascular actions and a low risk for severe adverse events 7.

Key Findings

• Semaglutide is not associated with an increased risk of acute pancreatitis compared to placebo 3.
• GLP-1RA users, including those taking semaglutide, have a lower risk of recurrent acute pancreatitis compared to non-users 5.
• Semaglutide has a favorable safety profile, with mostly mild-to-moderate and transient gastrointestinal disturbances, and an increased risk of biliary disease (cholelithiasis) 7.

Study Limitations

• The meta-analysis had a limited number of studies and patients, which may affect the generalizability of the results 3.
• The case report presented a single patient, which may not be representative of the larger population 4.
• The retrospective cohort study used a database platform, which may be subject to biases and limitations 5.