DISCLAIMER: This publication is aimed at health professionals. The information is meant to provide updates on medication safety issues, and not as a substitute for clinical judgement. While reasonable care has been taken to verify the accuracy of the information at the time of publication, NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.

 

Overview of Product(s) 

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of drugs that exert their therapeutic effects through multiple mechanisms, including enhancement of insulin secretion, promotion of β-cell proliferation, suppression of glucagon secretion, and delayed gastric emptying.^1,2 Dual GLP-1/GIP (glucose-dependent insulinotropic polypeptide) receptor agonists such as tirzepatide target both GLP-1 and GIP receptors, resulting in synergistic metabolic effects.³ Both GLP-1 RAs and GLP-1/GIP RAs have demonstrated efficacy in improving glycaemic control and promoting weight loss.^1,3 

There are 40 products from these classes registered with the Drug Control Authority (DCA), available as injectable and oral formulations.⁴ The GLP-1 RAs comprise dulaglutide (2), liraglutide (3), lixisenatide (2), and semaglutide (15), while the GLP-1/GIP RA comprises tirzepatide (18).

 

Overview of Safety Concern 

Intestinal obstruction is characterised by impaired transit of intestinal contents resulting from mechanical blockage or functional bowel paralysis.⁵ It may affect the small intestine or colon and vary in severity from partial to complete obstruction, with vascular compromise in some cases. Intestinal obstruction typically presents with abdominal pain, abdominal distension, nausea, vomiting, and constipation.^1,3 If not promptly managed, serious complications such as intestinal perforation, sepsis, aspiration, and death may occur.

 

Source of Safety Concern 

The National Pharmaceutical Regulatory Agency (NPRA) received information from the United States Food and Drug Administration (US FDA) regarding the risk of intestinal obstruction associated with active ingredients listed under GLP-1 RAs, which include tirzepatide, a dual GLP-1/GIP receptor agonist.⁶ The US FDA identified this potential safety signal during the surveillance of post-marketing data in the FDA Adverse Event Monitoring System (AEMS) database. Subsequently, the US FDA revised the product information for the affected products to reflect the risk of intestinal obstruction.^7-11

 

Background of Safety Issue 

Gastrointestinal (GI) adverse effects such as nausea and vomiting are commonly associated with GLP-1 RAs due to their actions on both the GI tract and the central nervous system.¹² More serious GI complications, including ileus and intestinal obstruction, have also been described in case reports. 

The pathophysiological mechanisms underlying GLP-1 RA-associated intestinal obstruction are multifactorial.¹ Activation of GLP-1 receptors throughout the GI tract reduces peristalsis, delays gastric emptying, and alters the migrating motor complex, thereby prolonging gastric and small-bowel transit and potentially increasing the risk of gastroparesis and intestinal obstruction, particularly in individuals with pre-existing dysmotility. GLP-1 RAs may also suppress sympathetic nervous system activity via GLP-1 receptors on splanchnic nerves and the sympathetic nerve branch of Auerbach’s plexus, further reducing intestinal motility and delaying gastric emptying.^1,3 

A published cohort study evaluating the risk of intestinal obstruction associated with GLP-1 RAs found an increased risk compared with SGLT-2 inhibitors (HR: 1.69, 95% CI: 1.04–2.74).² The risk increased with longer treatment duration, peaking after approximately 1.6 years of use (HR: 3.48, 95% CI: 1.79–6.79) before declining thereafter. An analysis of reports of intestinal obstruction associated with GLP-1 RAs in the World Health Organisation (WHO) global database found higher reporting of this adverse event compared with other diabetes drugs (ROR: 3.05, 95% CI: 2.54–3.66).¹³

 

Local Adverse Drug Reaction Reports¹⁴ 

To date, the NPRA has received 572 reports with 1,227 adverse events suspected to be related to GLP-1 and GLP-1/GIP RA-containing products. The most frequently reported adverse events were nausea (177), vomiting (121), and diarrhoea (53). Although there have been no reported cases of intestinal obstruction, adverse events potentially associated with this condition have been reported. These include abdominal distension, constipation, and infrequent bowel movements. Further details are summarised in the table below:

 

No.	Active ingredient	No. of reports	No. of adverse events	Adverse events potentially related to intestinal obstruction
1	Liraglutide	302	656	Constipation (22), abdominal distension (7), infrequent bowel movements (4), delayed gastric emptying (1)
2	Semaglutide	128	269	Abdominal distension (7), constipation (3), impaired gastric emptying (1)
3	Dulaglutide	76	143	Constipation (4)
4	Tirzepatide	50	131	Constipation (2)
5	Lixisenatide	16	28	None

 

 

Advice for Health Care Professionals

• While NPRA is still reviewing this safety issue, be aware of the risk of intestinal obstruction associated with the use of GLP-1 and GLP-1/GIP RAs.
• Exercise caution when prescribing these products to patients with a history of gastrointestinal motility disorders. Close monitoring should be considered.
• Review patients’ concomitant medications that could exacerbate this risk, such as opioids, anticholinergics, or other agents that may reduce gastrointestinal motility.
• Consider discontinuation, dose reduction, or switching to an alternative therapy based on individual assessment of the therapeutic benefits and risks.
• Educate patients to seek medical attention if they experience symptoms suggestive of intestinal obstruction, such as abdominal pain, abdominal distension, nausea, vomiting, and constipation.
• Report all adverse events suspected to be related to the use of GLP-1 and GLP-1/GIP RAs to NPRA.

  

References:

1. Jones M, Cappola JJ. GLP-1 Receptor Agonists in Diabetes and Obesity: A Case Report and Review of Bowel Obstruction Risks and Management. Cureus. 2025 Apr 8;17(4):e81891. Available from: https://doi.org/10.7759/cureus.81891
2. Faillie JL, Yin H, Yu OHY, Herrero A, Altwegg R, Renoux C, Azoulay L. Incretin-Based Drugs and Risk of Intestinal Obstruction among Patients with Type 2 Diabetes. Clin Pharmacol Ther. 2022 Jan;111(1):272-282. Available from: https://doi.org/10.1002/cpt.2430
3. Nahar S, Maybee N, Tamanna N, Sadat A, Khanam F, Begum R, Akther S, Khan MS, Sonia SN, Hasan N. Severe Small-Bowel Obstruction in a High-Risk Patient on Long-Term Tirzepatide Therapy: A Case Report. Cureus. 2025 Dec 10;17(12):e98935. Available from: https://doi.org/10.7759/cureus.98935
4. National Pharmaceutical Regulatory Agency (NPRA). QUEST3+ Product Search [Internet]. 2026 [cited 2026 Jul 21]. Available from: https://quest3plus.bpfk.gov.my/pmo2/index.php
5. Alashaby SS, Gilan WM, Al-Absy TA, Al-Magedi AAS. Etiology, Clinical Profile, Management, and Outcomes of Intestinal Obstruction in a Resource-Limited Setting: A Prospective Study. Sci Rep. 2026 Mar 27;16:10962. Available from: https://doi.org/10.1038/s41598-026-45380-w
6. United States Food and Drug Administration (US FDA). April - June 2025 New Safety Information or Potential Signals of Serious Risks Identified from the FDA Adverse Event Monitoring System (AEMS) [Internet]. 2026 Feb 4 [cited 2026 May 5]. Available from: https://www.fda.gov/drugs/fda-adverse-event-monitoring-system-aems/april-june-2025-new-safety-information-or-potential-signals-serious-risks-identified-fda-adverse
7. United States Food and Drug Administration (US FDA). Drug Safety-related Labeling Changes (SrLC). Dulaglutide. 2026 Mar 3 [cited 2026 Jul 21]. Available from: https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm?event=searchdetail.page&DrugNameID=816
8. United States Food and Drug Administration (US FDA). Drug Safety-related Labeling Changes (SrLC). Liraglutide. 2025 Oct 14 [cited 2026 Jul 21]. Available from: https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm?event=searchdetail.page&DrugNameID=438
9. United States Food and Drug Administration (US FDA). Drug Safety-related Labeling Changes (SrLC). Lixisenatide. 2026 Mar 12 [cited 2026 Jul 21]. Available from: https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm?event=searchdetail.page&DrugNameID=2517
10. United States Food and Drug Administration (US FDA). Drug Safety-related Labeling Changes (SrLC). Semaglutide. 2025 Oct 14 [cited 2026 Jul 21]. Available from: https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm?event=searchdetail.page&DrugNameID=2183
11. United States Food and Drug Administration (US FDA). Drug Safety-related Labeling Changes (SrLC). Tirzepatide. 2025 Dec 19 [cited 2026 May 5]. Available from: https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm?event=searchdetail.page&DrugNameID=2823
12. Diraviam S, Tait C Jr. S4137 Beyond Nausea: A Case of Colonic Bowel Obstruction Linked to GLP-1 Agonist Use. The Am J Gastroenterol. 2025 Oct 1;120(10S2):S885. Available from: https://doi.org/10.14309/01.ajg.0001144008.40955.ab
13. Gudin B, Ladhari C, Robin P, Laroche ML, Babai S, Hillaire-Buys D, Faillie JL. Incretin-based drugs and Intestinal Obstruction: A Pharmacovigilance Study. Therapie. 2020;75(6):641-647. Available from: https://doi.org/10.1016/j.therap.2020.02.024
14. National Pharmaceutical Regulatory Agency (NPRA). The Malaysian National ADR Database (QUEST) [Internet]. 2026 [cited 2026 Jul 21]. Available from: https://www.npra.gov.my (access restricted)

 

Written by: Wo Wee Kee

Reviewed/Edited by: Lim Sze Gee, Dr Rema Panickar, Noor'ain Shamsuddin, Norleen Mohamed Ali