Can Ozempic (semaglutide) increase the risk of needing a cholecystectomy due to gallbladder disease?

Ozempic (Semaglutide) and Risk of Cholecystectomy Due to Gallbladder Disease

Yes, Ozempic (semaglutide) can increase the risk of needing a cholecystectomy due to gallbladder disease, as it is specifically listed as a potential adverse effect in clinical guidelines and the FDA drug label. 1, 2

Gallbladder Complications Associated with Semaglutide

Evidence from Guidelines and Drug Label

• According to the 2024 American Diabetes Association Standards of Care, semaglutide may cause "cholelithiasis and gallstone-related complications" 1
• The FDA drug label for Ozempic specifically notes that cholelithiasis was reported in 1.5% and 0.4% of patients treated with semaglutide 0.5 mg and 1 mg, respectively, while it was not reported in placebo-treated patients 2
• The American Gastroenterological Association (AGA) clinical practice guideline specifically mentions that GLP-1 receptor agonists, including semaglutide, have been associated with increased risk of gallbladder disease 1

Mechanism and Risk Factors

• Rapid weight loss, which commonly occurs with semaglutide (9.6% weight loss from baseline with 2.4 mg weekly dose), is a known risk factor for gallstone formation 1
• The risk appears to be dose-dependent, with higher rates of cholelithiasis at higher doses of semaglutide 2
• The risk may be further increased in patients who:
  • Have pre-existing gallstones
  • Experience rapid weight loss
  • Have obesity or type 2 diabetes (common indications for semaglutide)

Clinical Implications and Management

Monitoring Recommendations

• Patients starting semaglutide should be informed about the potential risk of gallbladder disease
• Consider baseline ultrasound in patients with risk factors for gallbladder disease
• Monitor for symptoms of gallbladder disease including:
  • Right upper quadrant pain
  • Nausea and vomiting after fatty meals
  • Referred pain to the right shoulder
  • Fever (if complications like cholecystitis develop)

Management Approach

1. For patients without pre-existing gallstones:

   • Routine prophylactic cholecystectomy is not recommended 1
   • Monitor for symptoms of gallbladder disease

2. For patients with asymptomatic gallstones:

   • Conservative management is generally appropriate 1, 3
   • Only 3.4% of patients with asymptomatic gallstones required cholecystectomy within 12 months in a prospective study of bariatric surgery patients 3

3. For patients who develop symptomatic gallbladder disease:

   • Prompt surgical evaluation for possible cholecystectomy 1
   • Laparoscopic cholecystectomy is the standard of care for symptomatic gallstone disease 1

Balancing Benefits and Risks

The decision to use semaglutide should balance its benefits (significant weight loss, improved glycemic control, cardiovascular benefits) against the risk of gallbladder disease:

• For patients with obesity or type 2 diabetes, the metabolic benefits of semaglutide may outweigh the risk of gallbladder complications
• For patients with a history of gallbladder disease, closer monitoring may be warranted
• The risk of surgical complications from cholecystectomy is generally low (2-8% morbidity) but increases with comorbidities 1

Common Pitfalls to Avoid

• Failure to inform patients: Patients should be counseled about the risk of gallbladder disease when starting semaglutide
• Unnecessary cholecystectomy: Not all patients with gallstones require surgery; asymptomatic gallstones can often be managed conservatively 1, 3
• Delayed diagnosis: Attributing all abdominal symptoms to GI side effects of semaglutide rather than considering gallbladder disease
• Overlooking risk factors: Patients with rapid weight loss or pre-existing gallstones may need closer monitoring

In conclusion, while semaglutide is an effective medication for weight management and glycemic control, clinicians should be aware of the increased risk of gallbladder disease and potential need for cholecystectomy, and monitor patients accordingly.