Can Mounjaro (tirzepatide) cause cholecystitis?

Mounjaro (Tirzepatide) and Cholecystitis Risk

Yes, Mounjaro (tirzepatide) can cause cholecystitis and other biliary diseases, and the American Diabetes Association guidelines explicitly recommend evaluating for gallbladder disease if cholelithiasis or cholecystitis is suspected, with avoidance of use in at-risk individuals. 1

Evidence for Biliary Disease Risk

The association between tirzepatide and biliary complications is well-established through multiple lines of evidence:

• Tirzepatide increases the risk of gallbladder/biliary diseases by 52% (RR = 1.52; 95% CI: 1.17-1.98) and cholelithiasis specifically by 67% (RR = 1.67; 95% CI: 1.14-2.44) compared to placebo or other hypoglycemic drugs. 2 This meta-analysis of 12 high-quality randomized controlled trials involving 12,351 patients provides the strongest current evidence for this association.

• The mechanism likely relates to rapid weight loss induced by tirzepatide, which is a known risk factor for gallstone formation and subsequent cholecystitis. 3 Tirzepatide produces very high weight loss compared to other diabetes medications. 1

• Importantly, the risk appears independent of dose—subgroup analysis found no dose-response relationship between different tirzepatide doses (5 mg, 10 mg, or 15 mg) and biliary disease risk. 2

Clinical Incidence and Severity

While the relative risk is elevated, the absolute incidence remains low:

• Rates of cholecystitis and cholelithiasis are extremely low (≤1%) across all doses of tirzepatide in clinical trials. 4 This represents rare but clinically significant events that require vigilance.

• The low absolute rates should not diminish clinical concern, as cholecystitis can lead to serious morbidity requiring urgent surgical intervention. 3

Guideline-Based Management Algorithm

For patients WITHOUT known gallbladder disease:

• Tirzepatide can be initiated with appropriate patient counseling about warning signs (right upper quadrant pain, nausea, vomiting, fever). 3
• Consider baseline gallbladder ultrasound to document stone burden before starting therapy, particularly in patients with additional risk factors (obesity, rapid weight loss history, female sex, age >40). 3
• Monitor for biliary symptoms during treatment and check GGT in addition to standard liver enzymes if symptoms develop. 3

For patients WITH asymptomatic cholelithiasis:

• Greater caution is warranted, as rapid weight loss from tirzepatide compounds the baseline risk of stone-related complications. 3
• Cholecystectomy should be strongly considered before initiating tirzepatide. 3
• If proceeding without surgery, intensive patient education and close monitoring are mandatory. 3

For patients WITH symptomatic cholelithiasis or acute cholecystitis:

• Tirzepatide represents a temporary contraindication and should be avoided until the acute condition is resolved. 3
• Discontinue tirzepatide immediately if acute gallbladder disease is confirmed. 1, 3
• Arrange urgent surgical consultation for definitive management. 3

Common Pitfalls to Avoid

• Do not dismiss mild right upper quadrant discomfort as simple GI side effects. While nausea and diarrhea are the most common adverse effects of tirzepatide (occurring in 39-49% of patients depending on dose), new-onset right upper quadrant pain warrants biliary evaluation. 4

• Do not continue tirzepatide if pancreatitis is suspected. The guidelines explicitly state to discontinue if pancreatitis is suspected, and acute pancreatitis can coexist with or mimic cholecystitis. 1

• Remember that tirzepatide may impair oral drug absorption during dose titration, including oral contraceptives, which could theoretically affect other medications used to manage biliary symptoms. 1

Comparison to Other GLP-1 Receptor Agonists

The biliary disease risk is a class effect of GLP-1 receptor agonists, not unique to tirzepatide:

• The American Diabetes Association guidelines note that GLP-1 RAs as a class require evaluation for gallbladder disease if cholelithiasis or cholecystitis is suspected, with avoidance in at-risk individuals. 1
• Tirzepatide, as a dual GIP/GLP-1 receptor agonist with very high weight loss efficacy, may theoretically pose higher risk than single GLP-1 agonists, though head-to-head biliary complication data are limited. 1