What are the recommendations for using Glucagon-like peptide-1 (GLP-1) receptor agonists in patients with bowel obstruction?

GLP-1 Receptor Agonists in Patients with Bowel Obstruction

GLP-1 receptor agonists are contraindicated in patients with active bowel obstruction and should be discontinued immediately if bowel obstruction is suspected or diagnosed. 1

Mechanism of Concern

GLP-1 receptor agonists significantly delay gastric emptying through vagal nerve-mediated pathways, reducing phasic gastric contractions and increasing both fasting and postprandial gastric volumes. 2 This mechanism creates a physiological environment that can worsen or precipitate bowel obstruction, particularly in patients with pre-existing gastrointestinal motility disorders. 2

Clinical Evidence of Risk

The American Society of Anesthesiologists explicitly identifies gastrointestinal obstruction as a condition that increases aspiration risk and requires clinical judgment when considering procedures in patients on GLP-1 receptor agonists. 1 This classification places bowel obstruction in the same high-risk category as gastroparesis, previous gastric surgery, and acute intra-abdominal processes. 1

Real-World Case Reports

Multiple case reports document serious complications:

• A 30-year-old woman developed food-induced small bowel obstruction requiring laparoscopic surgery after consuming kelp while on semaglutide 1.0 mg weekly. 3
• A 52-year-old woman without any surgical history developed functional small bowel obstruction following dose escalation of tirzepatide (Zepbound), with no other conventional risk factors present. 4

Epidemiological Data Shows Conflicting Results

The evidence on chronic risk is contradictory:

• A UK study found GLP-1 receptor agonists associated with increased intestinal obstruction risk compared to SGLT-2 inhibitors (HR: 1.69,95% CI: 1.04-2.74), with the highest risk after 1.6 years of use (HR: 3.48). 5
• However, a larger Scandinavian study across three countries found no statistically significant increased risk (adjusted HR: 0.83,95% CI: 0.69-1.01). 6
• A U.S. retrospective cohort of over 1.2 million patients found no increased risk compared to other anti-diabetic medications except for reduced risk versus insulins. 7

Management Algorithm for Patients with Bowel Obstruction

If Patient Presents with Active Bowel Obstruction:

1. Immediately discontinue the GLP-1 receptor agonist regardless of indication (diabetes or weight loss). 1

2. Document the following risk factors: 1, 8

   • Specific GLP-1 agent, dose, and last administration date
   • Duration of therapy and any recent dose escalations
   • Presence of nausea, vomiting, or abdominal distention
   • Co-prescribed medications that delay gastric emptying (opioids, proton pump inhibitors, tricyclic antidepressants)
   • Previous gastro-oesophageal or abdominal surgery
   • Recent alcohol or cannabis use

3. Assume the stomach is full when planning any procedural intervention requiring sedation or anesthesia. 1

4. Implement aspiration risk reduction strategies: 1, 8

   • Use rapid sequence intubation for any procedure requiring general anesthesia
   • Consider point-of-care gastric ultrasound to assess residual gastric contents
   • Consider pre-emptive gastric decompression in very high-risk patients
   • Administer prokinetic drugs (metoclopramide or erythromycin) pre-operatively

Before Restarting GLP-1 Receptor Agonists Post-Resolution:

Do not restart GLP-1 receptor agonists until bowel obstruction has completely resolved and normal bowel function is confirmed. 1

For patients with diabetes requiring the medication:

• Consult endocrinology for alternative glycemic management during the acute phase. 1, 8
• Consider whether the patient has underlying gastroparesis or motility disorders that would make GLP-1 receptor agonists permanently inappropriate. 2

For patients using GLP-1 receptor agonists for weight loss:

• Strongly consider permanent discontinuation given the risk-benefit profile in non-diabetic patients. 1

Critical Pitfalls to Avoid

Do not assume standard fasting times are adequate. Multiple studies demonstrate retained gastric contents despite 8-12 hour fasting periods in patients on GLP-1 receptor agonists. 1 In one study, 7 of 10 patients on semaglutide had solids in the stomach after a 10-hour fast. 1

Do not rely on short discontinuation periods. Discontinuation for 7 days did not decrease the prevalence of retained gastric contents for long-acting agents. 1 The half-life of semaglutide is approximately 7 days, requiring 21 days (three half-lives) to clear 88% of the drug. 1, 8

Do not overlook the increased risk in patients who recently started or escalated doses. The case reports specifically involved patients who had recently increased doses or were on higher doses for weight loss. 3, 4