Can Glucagon-like peptide-1 (GLP-1) receptor agonists cause intestinal obstruction?

From the Guidelines

Yes, bowel obstruction can occur as a rare but serious side effect of GLP-1 receptor agonists like semaglutide, liraglutide, tirzepatide, and dulaglutide. These medications slow gastric emptying and intestinal motility, which can potentially lead to severe constipation and, in rare cases, intestinal blockage, as seen in studies where patients on GLP-1 receptor agonists had a higher incidence of gastric residue and food retention compared to the control group 1. Patients with pre-existing gastrointestinal conditions may be at higher risk. Warning signs of a potential bowel obstruction include severe constipation, persistent abdominal pain, abdominal distension, nausea, vomiting (especially if it contains fecal material), and inability to pass gas or stool. The mechanism relates to how GLP-1 agonists affect the digestive system by slowing gut motility to promote satiety and regulate blood sugar, as noted in a narrative review of clinical pharmacology and implications for peri-operative practice 1.

Some key points to consider:

• A single-centre prospective cohort study found that patients taking semaglutide had a higher risk of solids in the stomach on gastric ultrasound despite a 10 h fast, compared to the control group 1.
• Another study found that patients on GLP-1 receptor agonists had a higher incidence of retained gastric contents, defined as presence of solids, thick liquids or > 1.5 ml.kg-1 of clear liquids, compared to the control group 1.
• The use of GLP-1 receptor agonists has been associated with an increased risk of pulmonary aspiration under anaesthesia, which may be related to the delayed gastric emptying and increased gastric residue caused by these medications 1.
• If you experience symptoms suggesting bowel obstruction while taking a GLP-1 agonist, seek immediate medical attention as this condition requires prompt evaluation and may necessitate hospitalization, medication adjustment, or in severe cases, surgical intervention.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Bowel Obstruction as a Side Effect of GLP-1 Agonist

• The risk of bowel obstruction associated with GLP-1 agonists has been investigated in several studies 2, 3, 4, 5.
• A study published in 2022 found that GLP-1 receptor agonists (GLP-1 RAs) were associated with an increased risk of intestinal obstruction compared with SGLT-2 inhibitors, with a hazard ratio of 1.69 (95% CI: 1.04-2.74) 2.
• However, a systematic review and meta-analysis published in 2025 found that the use of GLP-1 RAs did not show an incremental risk of bowel obstruction or ileus compared to controls, although the studies had high heterogeneity (I2 = 94%) 3.
• A subgroup analysis in the same study revealed that liraglutide was associated with a significantly high risk of bowel obstruction or ileus (OR 3.0,95% CI 2.03-4.45; I2 = 0%) 3.
• Another study published in 2024 found that GLP-1RA exposure was not associated with an increased risk of ileus or intestinal obstruction in patients with inflammatory bowel disease (IBD) 4.
• An observational study published in 2023 found that GLP-1 RA liraglutide or DPP-4i sitagliptin did not significantly increase the incidence of inadequate bowel cleaning and gastrointestinal symptoms during bowel preparation, although liraglutide may increase the incidence of inadequate bowel preparation in patients with diabetic peripheral neuropathy (DPN) 5.
• Common adverse events associated with GLP-1-based therapies include gastrointestinal symptoms such as nausea, vomiting, obstipation, or diarrhea, which can often be mitigated by slow up-titration 6.