Can Mounjaro (tirzepatide) increase the risk of pancreatitis in patients with obesity and hypertriglyceridemia?

From the Guidelines

Mounjaro (tirzepatide) may increase the risk of pancreatitis in people with obesity and high triglycerides, and healthcare providers should evaluate baseline pancreatitis risk before prescribing the medication. Patients with obesity and high triglycerides already have an elevated risk of pancreatitis, and GLP-1 receptor agonists like Mounjaro have been associated with cases of acute pancreatitis in clinical trials and post-marketing reports 1. The medication works by mimicking incretin hormones that stimulate insulin secretion, which can affect pancreatic function.

Key Considerations

• The American Gastroenterological Association recommends using semaglutide 2.4 mg with lifestyle modifications for adults with obesity or overweight with weight-related complications, but notes that GLP-1 RAs have been associated with increased risk of pancreatitis and gallbladder disease 1.
• The American College of Cardiology suggests that patients with severe hypertriglyceridemia have a relatively high incidence of acute pancreatitis, and therapies should be implemented to reduce excesses in both chylomicrons and VLDL in severe hypertriglyceridemia 1.
• The Endocrine Society recommends initial treatment of patients with mild to moderate hypertriglyceridemia to include dietary counseling and weight loss in patients who are overweight or obese, and reduced intake of dietary fat and simple carbohydrates for patients with severe to very severe hypertriglyceridemia 1.
• The American Diabetes Association recommends evaluating for secondary causes of hypertriglyceridemia and considering medical therapy to reduce the risk of pancreatitis for individuals with fasting triglyceride levels ≥500 mg/dL 1.

Monitoring and Risk Assessment

During treatment with Mounjaro, patients should be alert for warning signs of pancreatitis such as severe abdominal pain radiating to the back, nausea, vomiting, or fever, and seek immediate medical attention if these occur. Healthcare providers may recommend monitoring pancreatic enzymes periodically, especially if patients have additional risk factors like gallstones or excessive alcohol consumption. The benefits of Mounjaro for weight management and metabolic improvement often outweigh this risk for most patients, but individual risk assessment is essential.

From the FDA Drug Label

5.2 Pancreatitis Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists. In clinical studies, 14 events of acute pancreatitis were confirmed by adjudication in 13 MOUNJARO-treated patients (0.23 patients per 100 years of exposure) versus 3 events in 3 comparator-treated patients (0.11 patients per 100 years of exposure). MOUNJARO has not been studied in patients with a prior history of pancreatitis. It is unknown if patients with a history of pancreatitis are at higher risk for development of pancreatitis on MOUNJARO After initiation of MOUNJARO, 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, discontinue MOUNJARO and initiate appropriate management.

Mounjaro and Pancreatitis Risk in Obesity and High Triglycerides:

• The FDA drug label reports that acute pancreatitis has been observed in patients treated with GLP-1 receptor agonists, including Mounjaro.
• The incidence of acute pancreatitis in Mounjaro-treated patients was 0.23 patients per 100 years of exposure, compared to 0.11 patients per 100 years of exposure in comparator-treated patients.
• However, the label does not provide specific information on the risk of pancreatitis in patients with obesity and high triglycerides.
• Key Points:
  • Mounjaro has been associated with an increased risk of acute pancreatitis.
  • The risk of pancreatitis in patients with obesity and high triglycerides is not explicitly stated in the label.
  • Patients should be carefully observed for signs and symptoms of pancreatitis after initiation of Mounjaro.
  • If pancreatitis is suspected, Mounjaro should be discontinued and appropriate management initiated 2.

From the Research

Mounjaro and Pancreatitis Risk

• The risk of pancreatitis associated with Mounjaro (tirzepatide) in patients with obesity and high triglycerides is not significantly increased, according to a systematic review and meta-analysis 3.
• The study found that compared to control groups, including basal insulin, selective GLP1-RA, and placebo, tirzepatide did not have a significantly increased risk of pancreatitis (RR 1.46, [95% CI] 0.59 to 3.61; I2 = 0.0%, p = 0.436) 3.
• However, the same study found that tirzepatide was associated with an increased risk of gallbladder or biliary disease compared to placebo or basal insulin (RR 1.97, [95% CI] 1.14 to 3.42; I2 = 0.0%, p = 0.558) 3.

Efficacy of Mounjaro in Obesity and Type 2 Diabetes

• Mounjaro has been shown to be effective in reducing body weight and improving glycemic control in patients with type 2 diabetes and obesity 4, 5, 6, 7.
• In the SURMOUNT-1 trial, tirzepatide resulted in substantial reductions in body weight (16.5% to 22.4%) over 72 weeks in people without diabetes 7.
• The SURPASS program and SURMOUNT-1 study suggest that tirzepatide is a promising treatment for type 2 diabetes and/or obesity management through dual agonism of gut hormones 7.

Safety Profile of Mounjaro

• The safety profile of tirzepatide is similar to that of GLP-1 receptor analogues, with common adverse events including gastrointestinal symptoms such as nausea, vomiting, diarrhea, and constipation 5, 7.
• The risk of pancreatitis and gallbladder or biliary disease associated with tirzepatide should be monitored in clinical practice, particularly in patients with a history of these conditions 3.