Should a patient on a GLP-1 (Glucagon-like peptide-1) receptor agonist stop the medication if they develop gallstones?

Management of Gallstones in Patients Taking GLP-1 Receptor Agonists

GLP-1 receptor agonists should not be routinely discontinued in patients who develop gallstones unless there are symptoms of biliary disease requiring intervention. 1

Understanding the Relationship Between GLP-1 RAs and Gallstones

GLP-1 receptor agonists (GLP-1 RAs) have been associated with an increased risk of gallbladder and biliary diseases. According to high-quality evidence:

• GLP-1 RAs may cause cholelithiasis (gallstones) and gallstone-related complications 1
• Meta-analysis data shows a 37% increased risk of gallbladder or biliary diseases with GLP-1 RA use 2
• The risk is higher with:
  • Higher doses of medication (56% increased risk)
  • Longer duration of use (40% increased risk)
  • When used primarily for weight loss (129% increased risk) 2

Clinical Decision Algorithm for Patients with Gallstones on GLP-1 RAs

1. Assess Symptom Status

For asymptomatic gallstones:

• Continue GLP-1 RA therapy
• Nearly 80% of gallstones are found incidentally and remain asymptomatic 3
• Regular monitoring for development of symptoms is appropriate

For symptomatic gallstones:

• Evaluate severity of symptoms (right upper quadrant or epigastric pain)
• Assess for complications such as cholecystitis, choledocholithiasis, or gallstone pancreatitis

2. Evaluate Risk-Benefit Profile

Consider the following factors when deciding whether to continue or discontinue GLP-1 RA therapy:

Benefits of continuing GLP-1 RA:

• Cardiovascular protection (reduced risk of major adverse cardiovascular events) 1, 4
• Glycemic control for patients with diabetes
• Weight management benefits
• Renal protection (reduced albuminuria, slower eGFR decline) 4

Risks of continuing GLP-1 RA:

• Potential for worsening gallstone disease
• Increased risk of requiring cholecystectomy (adjusted HR 2.08) 5

3. Management Approach Based on Clinical Presentation

For mild, intermittent biliary symptoms:

• Consider continuing GLP-1 RA therapy with close monitoring
• Manage pain with NSAIDs as needed
• Schedule follow-up ultrasonography to monitor gallstone status

For moderate to severe symptoms or complications:

• Consider temporary interruption of GLP-1 RA therapy until acute symptoms resolve
• Surgical consultation for possible cholecystectomy
• If cholecystectomy is performed, GLP-1 RA can generally be resumed after recovery

For patients requiring surgical intervention:

• If elective surgery is planned, consider holding GLP-1 RA for at least three half-lives before the procedure to reduce anesthesia-related risks 1
• For patients with diabetes, consult with endocrinology regarding alternative glycemic control during any period of GLP-1 RA interruption 1

Special Considerations

1. Patients on GLP-1 RAs for diabetes vs. weight loss:

   • For patients with diabetes, the cardiovascular and glycemic benefits may outweigh the gallstone risk
   • For patients using GLP-1 RAs solely for weight loss, consider alternative weight management strategies if gallstone symptoms are significant

2. Dose modification:

   • Consider dose reduction rather than complete discontinuation in patients with mild symptoms who derive significant benefit from GLP-1 RA therapy

3. Monitoring recommendations:

   • Patients with asymptomatic gallstones should be educated about symptoms of biliary colic and when to seek medical attention
   • Regular liver function tests may be appropriate for monitoring

Common Pitfalls to Avoid

1. Unnecessary discontinuation: Automatically stopping GLP-1 RA therapy for incidental, asymptomatic gallstones may deprive patients of important metabolic and cardiovascular benefits

2. Failure to recognize complications: Delayed recognition of serious biliary complications like cholangitis or gallstone pancreatitis can lead to poor outcomes

3. Inadequate perioperative management: For patients requiring cholecystectomy, failing to appropriately time GLP-1 RA discontinuation before surgery may increase anesthesia-related risks due to delayed gastric emptying 1

4. Overlooking alternative causes: Not all abdominal pain in patients on GLP-1 RAs is due to gallstones; consider other causes including gastroparesis from the medication itself

By following this structured approach, clinicians can appropriately manage patients who develop gallstones while on GLP-1 receptor agonist therapy, balancing the risks of biliary disease against the significant metabolic and cardiovascular benefits these medications provide.