From the Guidelines
Gallstones are not an absolute contraindication for GLP-1 receptor agonists, but caution is warranted due to the potential increased risk of gallbladder-related issues, as noted in the 2024 standards of care in diabetes 1.
Key Considerations
- Patients with a history of gallstones or gallbladder disease should discuss this with their healthcare provider before starting GLP-1 receptor agonists.
- GLP-1 agonists can potentially increase the risk of gallbladder-related issues because they slow gastric emptying and may reduce gallbladder contraction, which can promote gallstone formation.
- Some clinical studies have shown a slightly increased incidence of gallbladder events, including cholecystitis, in patients taking GLP-1 medications compared to control groups, as seen in the 2023 review of obesity management in adults 1.
Monitoring and Precautions
- If you already have gallstones, your doctor may recommend monitoring your gallbladder function while on these medications.
- Symptoms that should prompt immediate medical attention include severe upper abdominal pain, especially after meals, pain radiating to your back or right shoulder, nausea, vomiting, or yellowing of the skin.
- Weight loss itself, which commonly occurs with GLP-1 medications, can also temporarily increase the risk of gallstone formation as the body mobilizes fat stores, as mentioned in the 2019 update to the management of hyperglycemia in type 2 diabetes 1.
Medication-Specific Considerations
- The 2018 expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes and atherosclerotic cardiovascular disease notes that GLP-1 receptor agonists can be considered in patients with type 2 diabetes without established cardiovascular disease but with specific indicators of high risk 1.
- The 2019 scientific statement from the American Heart Association and the Heart Failure Society of America highlights the importance of considering the potential benefits and risks of GLP-1 receptor agonists in patients with heart failure, particularly those with heart failure with reduced ejection fraction 1.
From the FDA Drug Label
5.7 Acute Gallbladder Disease Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated
The presence of gallstones (cholelithiasis) is not a contraindication for the use of GLP-1 receptor agonists, such as liraglutide, but it may require monitoring and appropriate clinical follow-up 2.
From the Research
Gallstones and GLP-1 Receptor Agonists
- The use of GLP-1 receptor agonists may be associated with an increased risk of bile duct and gallbladder disease, including gallstones 3, 4, 5.
- A systematic review and meta-analysis of randomized clinical trials found that GLP-1 receptor agonist treatment was associated with increased risks of gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss 4.
- The exact mechanism of how GLP-1 receptor agonists increase the risk of gallstones is not fully understood, but it may be related to the effects of GLP-1 on gallbladder motility and the bile acid-TGR5-L cell-GLP-2 axis 5.
- GLP-1 receptor agonists are not contraindicated in patients with gallstones, but physicians should be aware of the potential increased risk of gallbladder disease when prescribing these drugs 3, 6.
Key Findings
- GLP-1 receptor agonists may increase the risk of gallbladder disease, including gallstones 3, 4.
- The risk of gallbladder disease may be higher with longer duration of use and higher doses of GLP-1 receptor agonists 4.
- GLP-1 receptor agonists should be used with caution in patients with a history of gallbladder disease or pancreatitis 6.
- Further research is needed to fully understand the relationship between GLP-1 receptor agonists and gallstones 4, 5.