From the Guidelines
GLP-1 medications can potentially cause cholestasis even in someone without a gallbladder, though it's less common than in those with intact gallbladders. Medications like semaglutide and liraglutide have been associated with biliary disorders, including cholelithiasis and gallstone-related complications 1. Without a gallbladder, you can't develop gallstones, but cholestasis can still occur due to bile duct narrowing or inflammation. GLP-1 medications slow gastric emptying and intestinal motility, which can affect bile flow and potentially lead to cholestasis.
Key Points to Consider
- Symptoms to watch for include yellowing of skin or eyes, dark urine, light-colored stools, right upper abdominal pain, and unexplained fatigue.
- If you experience these symptoms while taking a GLP-1 medication, contact your healthcare provider immediately.
- Regular liver function tests may be recommended during treatment, especially if you have pre-existing liver conditions or are at higher risk for biliary issues.
Safety Concerns
- GLP-1RAs may also increase the risk of gallbladder disease, including acute cholecystitis 1.
- Caution should be used in patients with prior gastric surgery.
- GLP-1RAs can lead to elevations in heart rate and may increase the risk of pancreatitis, although the causal link between this class of drugs and either pancreatitis or pancreatic cancer has not been identified by the FDA and the European Medicines Agency 1.
From the FDA Drug Label
Hepatobiliary: Elevations of liver enzymes, hyperbilirubinemia, cholestasis, cholecystitis, cholelithiasis requiring cholecystectomy, hepatitis 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. 5.9 Acute Gallbladder Disease Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and post-marketing.
Cholestasis Risk: The FDA drug labels for liraglutide 2 and exenatide 3 report postmarketing cases of cholestasis.
- Key Points:
- Cholestasis has been reported in patients taking GLP-1 receptor agonists.
- The labels do not provide specific information on the risk of cholestasis in post-cholecystectomy patients.
- Clinical Decision: Given the reported cases of cholestasis, it is possible that a GLP-1 medication could cause cholestasis in a post-cholecystectomy patient. However, the available data do not provide a clear answer to this question. As a result, caution should be exercised when prescribing GLP-1 medications to post-cholecystectomy patients, and monitoring for signs of cholestasis is recommended.
From the Research
GLP-1 Medication and Cholestasis in Post-Cholecystectomy Patients
- The use of GLP-1 receptor agonists may be associated with an increased risk of bile duct and gallbladder disease, including cholestasis, as suggested by a study published in 2016 4.
- This study found that current use of GLP-1 analogues was associated with an increased risk of bile duct and gallbladder disease compared to current use of at least 2 oral antidiabetic drugs, with an adjusted hazard ratio of 1.79 (95% CI, 1.21-2.67) 4.
- Another study published in 2017 found that GLP-1 analogues exenatide and liraglutide exerted an inhibitory effect on the early phase of liver regeneration after partial hepatectomy in rats, which may be relevant to the development of cholestasis in post-cholecystectomy patients 5.
- However, it is essential to note that the evidence is not entirely consistent, and other studies have not found a significant association between GLP-1 receptor agonists and an increased risk of pancreatitis or other adverse events, including cholestasis 6, 7, 8.
- The potential side effects of GLP-1 agonists, including cholestasis, should be carefully considered and monitored in post-cholecystectomy patients, particularly those with a history of bile duct or gallbladder disease 4, 8.