What are the risks of gallbladder disease associated with Ozempic (semaglutide)?

From the Guidelines

Ozempic (semaglutide) has been associated with an increased risk of gallbladder disease, including gallstones (cholelithiasis), inflammation of the gallbladder (cholecystitis), and biliary disease, as reported in the most recent study from 2024 1. The risks appear to be related to rapid weight loss and changes in bile composition that occur during treatment. Patients taking Ozempic may experience a higher risk of developing gallbladder problems compared to those not using the medication.

Key Points to Consider

• The risk seems to increase with higher doses and longer duration of treatment, particularly in patients who lose weight rapidly, as noted in the 2023 study 1.
• Common symptoms of gallbladder issues include upper right abdominal pain, nausea, vomiting, and in some cases, jaundice (yellowing of the skin or eyes).
• Patients with a history of gallbladder disease should discuss this with their healthcare provider before starting Ozempic, as cautioned in the 2023 study 1.
• Those already taking the medication should be vigilant about reporting any symptoms suggestive of gallbladder problems.
• The underlying mechanism likely involves changes in cholesterol metabolism and bile composition during weight loss, which can promote gallstone formation, as discussed in the 2024 study 1.
• Gradual rather than rapid weight loss may help reduce this risk, though this needs to be balanced against the medication's therapeutic benefits.

Recommendations for Clinical Practice

• Healthcare providers should carefully weigh the benefits and risks of Ozempic in patients with a history of gallbladder disease or those at high risk of developing gallbladder problems.
• Patients taking Ozempic should be monitored closely for signs and symptoms of gallbladder disease, and the medication should be discontinued if pancreatitis is suspected, as advised in the 2024 study 1.
• Further research is needed to fully understand the relationship between Ozempic and gallbladder disease, but for now, caution and close monitoring are recommended, as suggested by the 2023 study 1.

From the FDA Drug Label

Cholelithiasis was reported in 1.5% and 0.4% of patients-treated with OZEMPIC 0.5 mg and 1 mg, respectively. Cholelithiasis was not reported in placebo-treated patients. The risk of gallbladder disease, specifically cholelithiasis, is associated with Ozempic (semaglutide) use, with reported frequencies of 1.5% and 0.4% for the 0.5 mg and 1 mg doses, respectively 2.

• Key points:
  • Cholelithiasis was not reported in placebo-treated patients.
  • The risk of gallbladder disease may be a consideration for patients taking Ozempic.

From the Research

Risks of Gallbladder Disease Associated with Ozempic (Semaglutide)

The use of Ozempic (semaglutide), a glucagon-like peptide-1 receptor agonist, has been associated with an increased risk of gallbladder disease. Key findings include:

• A systematic review and meta-analysis of randomized clinical trials found that the use of GLP-1 receptor agonists, including semaglutide, was associated with an increased risk of gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss 3.
• A population-based cohort study found that the use of GLP-1 analogues, including semaglutide, was associated with an increased risk of bile duct and gallbladder disease, including cholecystectomy 4.
• Research on the effects of GLP-1 on gallbladder motility suggests that GLP-1 receptor agonist treatment may prolong the refilling phase of the gallbladder, potentially increasing the risk of gallbladder diseases 5.

Specific Risks Associated with Semaglutide

Studies have reported the following specific risks associated with semaglutide:

• Increased risk of biliary disease, including cholelithiasis 6.
• Gastrointestinal side effects, including nausea, vomiting, and diarrhea 7, 6.
• Potential risk of pancreatic safety issues, including pancreatitis and pancreatic cancer, although definitive conclusions cannot be drawn due to low incidence of these conditions 6.

Factors Influencing the Risk of Gallbladder Disease

The risk of gallbladder disease associated with semaglutide may be influenced by:

• Dose: Higher doses of semaglutide may be associated with an increased risk of gallbladder disease 3.
• Duration of use: Longer durations of semaglutide use may be associated with an increased risk of gallbladder disease 3.
• Indication: Semaglutide use for weight loss may be associated with a higher risk of gallbladder disease compared to use for type 2 diabetes 3.