What are the considerations for using Mounjaro (tirzepatide) in patients with cholelithiasis (gallstones)?

Management of Mounjaro (Tirzepatide) in Patients with Cholelithiasis

Mounjaro (tirzepatide) can be used in patients with cholelithiasis, but requires careful monitoring for gallstone-related complications as GLP-1 receptor agonists may increase the risk of biliary disease.

Risk Assessment and Considerations

Established Risk of Gallbladder Disease with GLP-1 RAs

• GLP-1 receptor agonists, including tirzepatide, have been associated with an increased risk of gallbladder and biliary diseases, including cholelithiasis and gallstone-related complications 1
• The 2025 American Diabetes Association Standards of Care specifically notes that GLP-1 RAs may cause cholelithiasis and gallstone-related complications 2
• Dual GIP and GLP-1 receptor agonists like tirzepatide carry a specific caution regarding biliary disease, with recommendations to evaluate for gallbladder disease if cholelithiasis or cholecystitis is suspected 2

Incidence of Gallstone Complications

• Clinical trials of tirzepatide showed extremely low rates (≤1%) of cholelithiasis and cholecystitis across all doses 3
• The risk appears to be dose-dependent, with higher doses potentially carrying greater risk

Management Algorithm for Patients with Cholelithiasis on Tirzepatide

For Asymptomatic Gallstones:

1. Continue tirzepatide therapy with regular monitoring
2. Educate patient about symptoms of biliary colic and when to seek medical attention
3. Consider periodic liver function tests to monitor for complications
4. No need for routine discontinuation in the absence of symptoms 1

For Mildly Symptomatic Gallstones:

1. Consider dose reduction rather than complete discontinuation if patient derives significant benefit from tirzepatide 1
2. Implement dietary modifications (low-fat diet)
3. Monitor more frequently for progression of symptoms
4. Consider referral to gastroenterology or surgery for evaluation

For Symptomatic Gallstones Requiring Intervention:

1. Discontinue tirzepatide if surgical intervention is planned 1
2. Hold tirzepatide for at least three half-lives before any surgical procedure to reduce anesthesia-related risks
3. For patients with diabetes, consult endocrinology for alternative glycemic control during tirzepatide interruption
4. After successful treatment of gallstone disease, tirzepatide can be restarted with careful monitoring

Special Considerations

Perioperative Management

• If cholecystectomy is required, tirzepatide should be temporarily discontinued
• The medication's effects on gastric emptying may complicate anesthesia
• Restart tirzepatide after recovery from surgery with appropriate dose titration

High-Risk Patients

• Patients with multiple risk factors for gallstone disease (obesity, rapid weight loss, female sex) should be monitored more closely
• Consider more frequent monitoring in patients with a history of gallstone disease
• The benefits of tirzepatide (glycemic control, weight management, cardiovascular protection) must be weighed against the risk of gallstone complications 1

Pitfalls and Caveats

• Do not confuse GI symptoms from tirzepatide itself (nausea, vomiting) with symptoms of gallstone complications
• Rapid weight loss from tirzepatide may independently increase the risk of gallstone formation
• Patients with asymptomatic gallstones should not undergo prophylactic cholecystectomy solely due to tirzepatide use
• Avoid assuming that all right upper quadrant pain in patients on tirzepatide is related to gallstones; consider other diagnoses including pancreatitis (another potential complication of GLP-1 RAs)

By following this structured approach, clinicians can appropriately manage patients with cholelithiasis who are candidates for or currently using tirzepatide, maximizing the benefits while minimizing the risks associated with this medication.