How does Ozempic (semaphorelin) cause pancreatitis?

From the Guidelines

Ozempic (semaglutide) can cause pancreatitis in some patients through several mechanisms, including stimulating insulin secretion, slowing gastric emptying, and potentially increasing pancreatic enzyme production, and patients with a history of pancreatitis, gallbladder disease, excessive alcohol consumption, and very high triglyceride levels are at higher risk. The drug works by mimicking GLP-1 (glucagon-like peptide-1), which stimulates insulin secretion and slows gastric emptying, as noted in the 2025 standards of care in diabetes 1. This action increases pancreatic enzyme production and can potentially lead to pancreatic inflammation. Additionally, Ozempic may cause gallstone formation due to weight loss and changes in bile composition, and these gallstones can block pancreatic ducts, triggering pancreatitis, as discussed in the context of weight management for the prevention and treatment of type 2 diabetes 1. The medication may also directly stimulate pancreatic acinar cells, causing them to release digestive enzymes that can damage pancreatic tissue. Some key points to consider when evaluating the risk of pancreatitis with Ozempic include:

• The medication's mechanism of action and its potential effects on the pancreas
• The patient's medical history, including any previous episodes of pancreatitis or gallbladder disease
• The patient's lifestyle factors, such as alcohol consumption and diet
• The importance of monitoring for symptoms of pancreatitis, such as severe upper abdominal pain, nausea, vomiting, and fever, as highlighted in the narrative review of clinical pharmacology and implications for peri-operative practice 1. If these symptoms occur while taking Ozempic, patients should seek immediate medical attention and discontinue the medication until evaluated by a healthcare provider. It is also important to note that the management of hyperglycemia in type 2 diabetes should be patient-centered, taking into account the individual's specific needs and risk factors, as emphasized in the position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) 1.

From the FDA Drug Label

5.2 Pancreatitis 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 exact mechanism of how Ozempic (semaglutide) causes pancreatitis is not directly stated in the label. However, pancreatitis is a reported adverse reaction in patients treated with Ozempic.

• 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 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

Ozempic (Semaglutide) and Pancreatitis

• The provided studies do not directly address how Ozempic (semaglutide) causes pancreatitis, as they focus on hypertriglyceridemia-induced acute pancreatitis and the treatment of this condition with insulin, heparin, and gemfibrozil 3, 4, 5, 6.
• However, one study mentions that GLP-1 receptor agonists, a class of drugs that includes semaglutide, have been associated with acute pancreatitis in several case reports and the US Food and Drug Administration pharmacovigilance database 7.
• The exact mechanism by which semaglutide may cause pancreatitis is not discussed in the provided studies, but it is known that GLP-1 receptor agonists can increase the risk of pancreatitis, possibly due to their effects on pancreatic beta-cell function and inflammation 7.

Hypertriglyceridemia-Induced Acute Pancreatitis

• Hypertriglyceridemia is a known cause of acute pancreatitis, and the provided studies discuss the treatment of this condition with insulin, heparin, and gemfibrozil 3, 4, 5, 6.
• The studies suggest that insulin therapy can be effective in reducing triglyceride levels and improving outcomes in patients with hypertriglyceridemia-induced acute pancreatitis 3, 5, 6.
• However, the relationship between semaglutide and pancreatitis is not directly addressed in these studies, and further research would be needed to fully understand the potential risks and mechanisms involved 7.