Can a patient with cholelithiasis use Mounjaro (tirzepatide)?

Can a Patient with Cholelithiasis Use Mounjaro (Tirzepatide)?

Mounjaro (tirzepatide) can be used in patients with existing cholelithiasis, but requires careful clinical judgment, close monitoring for gallbladder complications, and patient counseling about increased risk of acute gallbladder disease.

Evidence from FDA Labeling and Guidelines

The FDA label for Mounjaro explicitly addresses this concern 1:

• Acute gallbladder disease (cholelithiasis, biliary colic, cholecystectomy) occurred in 0.6% of tirzepatide-treated patients versus 0% of placebo patients in clinical trials 1
• If cholelithiasis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated 1
• The medication is not absolutely contraindicated in patients with existing gallstones, but requires vigilance 1

The 2025 American Diabetes Association guidelines note that for GLP-1 receptor agonists (the class most similar to tirzepatide): "Biliary disease: evaluate for gallbladder disease if cholelithiasis or cholecystitis is suspected; avoid use in at-risk individuals" 2. This suggests a cautious approach rather than absolute avoidance.

Risk Quantification from Recent Meta-Analysis

The most recent and highest-quality evidence comes from a 2025 meta-analysis of 12 randomized controlled trials involving 12,351 patients 3:

• Tirzepatide was associated with increased risk of cholelithiasis (RR = 1.67; 95% CI: 1.14-2.44) 3
• Tirzepatide was associated with gallbladder/biliary diseases (RR = 1.52; 95% CI: 1.17-1.98) 3
• No dose-response relationship was found between different tirzepatide doses and gallbladder disease risk 3

A 2023 systematic review found that rates of cholelithiasis and cholecystitis were extremely low (≤1%) across all doses of tirzepatide 4, suggesting the absolute risk remains small even if the relative risk is elevated.

Clinical Decision Algorithm

For Asymptomatic Cholelithiasis:

• Tirzepatide can be initiated with appropriate counseling 2, 1
• Inform patients about symptoms of acute cholecystitis (right upper quadrant pain, fever, nausea/vomiting) 1
• Consider baseline gallbladder ultrasound to document stone burden 5
• Monitor for development of biliary symptoms during treatment 1

For Symptomatic Cholelithiasis:

• Exercise greater caution - these patients are already at higher risk for complications 2
• Consider whether cholecystectomy should be performed before initiating tirzepatide 5
• If medication is needed urgently for diabetes/weight management, proceed with heightened surveillance 1
• Avoid use in patients with acute cholecystitis or recent biliary colic until resolved 2, 1

For Complicated Gallstone Disease:

• Do not initiate tirzepatide in patients with acute cholecystitis, choledocholithiasis, or cholangitis until these conditions are definitively treated 2, 1
• If common bile duct stones are present, ERCP with stone extraction should be performed first 5

Monitoring Strategy

• Educate patients to report right upper quadrant pain, nausea, vomiting, or fever immediately 1
• If biliary symptoms develop: obtain right upper quadrant ultrasound and liver function tests 5, 1
• Consider checking GGT in addition to standard liver enzymes, as it is more specific for biliary disease 5
• If acute gallbladder disease is confirmed, discontinue tirzepatide and arrange appropriate surgical consultation 1

Important Caveats

The mechanism of increased gallstone risk with GLP-1/GIP agonists relates to delayed gastric emptying and altered gallbladder motility 1, 6. This is a class effect seen with other incretin-based therapies 2.

The absolute risk remains low - even with a 67% relative risk increase, the baseline incidence is small enough that most patients will not develop complications 3, 4.

Rapid weight loss itself increases cholelithiasis risk 2, making it difficult to separate the drug effect from the weight loss effect in obesity treatment.

There is no evidence that pre-existing gallstones will be "mobilized" or cause acute complications simply from starting the medication 2, though vigilance is warranted.

The decision ultimately depends on weighing the substantial metabolic benefits of tirzepatide (HbA1c reduction, weight loss, cardiovascular benefits) against the modest increased risk of gallbladder complications in a patient who already has gallstones 2, 1, 3.