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 Products

Glucagon-like peptide-1 (GLP-1) receptor agonists act by mimicking endogenous GLP-1, a gastrointestinal hormone secreted following food ingestion.¹ Upon binding to GLP-1 receptors on pancreatic beta cells, these incretin mimetics stimulate insulin release in a glucose-dependent manner and simultaneously reduce alpha-cell glucagon secretion, improving glycaemic control. Another class comprises dual GLP-1/GIP (glucose-dependent insulinotropic polypeptide) receptor agonists, which target both human GLP-1 and GIP receptors.²

GLP-1 receptor agonists include exenatide, dulaglutide, liraglutide, lixisenatide, and semaglutide. These analogues exhibit high sequence homology to human GLP-1, with semaglutide demonstrating approximately 94% homology.³ Tirzepatide is a long-acting dual GLP-1/GIP receptor agonist that maintains high affinity for the GIP receptor while exhibiting a lower affinity for the GLP-1 receptor than native human GLP-1.²

Currently, there are 40 products from these classes registered in Malaysia. These products are mainly indicated for the management of type 2 diabetes mellitus, with selected products also approved for weight management and for cardiovascular risk reduction.⁴

 

Overview of Safety Concern

Acute pancreatitis is an inflammatory condition of the pancreas with highly variable clinical severity.⁵ It is categorised into three grades:

• Mild: Absence of organ failure and local or systemic complications.
• Moderately severe: Transient organ failure (resolving within <48 hours), or the presence of local or systemic complications.
• Severe: Persistent organ failure (lasting >48 hours), which frequently involves multiple organ systems.

 

Source of Safety Concern

The National Pharmaceutical Regulatory Agency (NPRA), through its global safety signal monitoring, noted that the United Kingdom Medicines and Healthcare Products Regulatory Agency (UK MHRA) had issued an update to strengthen warnings in the product information regarding the potential risk of severe acute pancreatitis, including rare reports of necrotising and fatal cases. This update was based on the MHRA review of 1,296 reports of pancreatitis associated with GLP-1 and dual GLP-1/GIP receptor agonists received between 2007 and October 2025.⁶

 

Background of the Safety Issue

Acute pancreatitis is primarily triggered by gallstones and alcohol consumption, while other triggers include medications, smoking, and genetics.⁷ Type 2 diabetes mellitus also represents a major risk factor, particularly in younger patients, with an increased risk observed in those with poor glycaemic control. Pre-existing comorbidities, such as elevated triglycerides, may further potentiate the risk of pancreatic inflammation.⁸

GLP-1 receptor agonists are hypothesised to cause overgrowth of cells lining the smaller ducts by activating receptors within the pancreatic islet beta cells and exocrine duct cells.⁹ This can lead to blockages and a subsequent build-up of pancreatic enzymes that induce acute pancreatic inflammation, severe enough to progress to necrosis.

Case reports indicate that acute pancreatitis associated with GLP-1 receptor agonists predominantly manifests as severe abdominal pain that may radiate directly to the back and occasionally to the flank, chest, and lower abdomen, often accompanied by nausea and vomiting.^7,9,10 Some patients also present with systemic signs of infection or distress, such as subjective fevers, chills, and diaphoresis.^7,9

Pancreatitis may be challenging to recognise in its early stages, as initial symptoms such as abdominal pain, nausea, or vomiting may be misattributed to common gastrointestinal side effects of GLP-1 and GLP-1/GIP agonist treatment or standard infections.⁶ A review of 39 published case reports up to December 2023 showed a wide variation in time to onset, ranging from within 24 hours of the first dose to 4 years, with a median onset of 2.5 months.⁷

 

Local Adverse Drug Reaction Reports¹¹

To date, NPRA has received a total of 504 reports containing 1,066 adverse events suspected to be associated with GLP-1 and dual GLP-1/GIP receptor agonists. Among these, one report each of pancreatitis and acute pancreatitis has been received, both suspected to be associated with semaglutide use. The most frequently reported events include nausea (183), vomiting (111), diarrhoea (37), dizziness (31), and headache (24).

 

Advice for Health Care Professionals

• Be alert to the risk of acute pancreatitis in patients receiving GLP-1 and dual GLP-1/GIP receptor agonists.
• Exercise caution when prescribing these products to patients with a history of pancreatitis.
• Advise patients to seek urgent medical attention if they develop severe and persistent abdominal pain that may radiate to the back, particularly if accompanied by nausea and vomiting.
• Enquire about GLP-1 or dual GLP-1/GIP receptor agonist use in any patient presenting with these symptoms, as privately prescribed therapies may not appear on the patient’s medical records.
• Discontinue the GLP-1 or GLP-1/GIP receptor agonist immediately if pancreatitis is suspected.
• Do not restart therapy if the diagnosis of pancreatitis is confirmed.
• Report all suspected adverse events related to GLP-1 or dual GLP-1/GIP receptor agonists to the NPRA.

 

References:

1. Tartaglia E, Bucci T, Rossi M, Rigutini AG, Askarinejad A, Alam U, et al. Risk of all-cause death and pancreatic events following GLP-1 RA initiation in people with obesity or type 2 diabetes: Observations from a federated research network. Cardiovasc Diabetol. 2025 Dec 1;24(1). Available from: https://doi.org/10.1186/s12933-025-02986-0
2. National Pharmaceutical Regulatory Agency (NPRA). The Malaysian Product Registration Database (QUEST). Mounjaro 2.5mg solution for injection in pre-filled pen local package insert [Internet]. 2025 March 17 [cited 2026 April 3]. Available from: https://www.npra.gov.my
3. National Pharmaceutical Regulatory Agency (NPRA). The Malaysian Product Registration Database (QUEST). Ozempic solution for injection in pre-filled pen local package insert [Internet]. 2025 March 17 [cited 2026 April 3]. Available from: https://www.npra.gov.my
4. National Pharmaceutical Regulatory Agency (NPRA). QUEST 3+ Product Search [Internet]. 2026 [cited 2026 Feb 4]. Available from: https://www.npra.gov.my
5. Wang CF, Tariq A, Subhash C. Acute pancreatitis continuing education activity [Internet]. 2025 Aug. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482468/?report=printable
6. Medicines and Healthcare products Regulatory Agency (UK MHRA). Drug Safety Update (DSU) GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists: Strengthened warnings on acute pancreatitis, including necrotising and fatal cases. 2026 Jan 29 [cited 2026 April 3]. Available from: https://www.gov.uk/drug-safety-update/glp-1-receptor-agonists-and-dual-glp-1-slash-gip-receptor-agonists-strengthened-warnings-on-acute-pancreatitis-including-necrotising-and-fatal-cases
7. Guo H, Guo Q, Li Z, Wang Z. Association between different GLP-1 receptor agonists and acute pancreatitis: Case series and real-world pharmacovigilance analysis. Front Pharmacol. 2024;15. Available from: https://doi.org/10.3389/fphar.2024.1461398
8. Yau A, Reisman T, Chen Z. Diabetes & glucose metabolism PSUN270 magnified risk of pancreatitis by GLP-1: A case of necrotizing pancreatitis in a patient on dulaglutide with baseline elevated triglycerides. J Endocrine Soc. 2022 Nov;6(Supplement_1):A399–400. Available from: https://doi.org/10.1210/jendso/bvac150.831
9. Grennan K, Borg C, Meneley A, Janitz T, Shuman M, Venegas C. Fatal, Fulminant, Necrotizing pancreatitis associated with recent tirzepatide Initiation. JCEM Case Reports. 2025 Jun 1;3(6). Available from: https://doi.org/10.1210/jcemcr/luaf087
10. Dagher C, Jailani M, Akiki M, et al. Semaglutide-induced acute pancreatitis leading to death after four years of use. Cureus. 2024 Sep 19;16(9):e69704. Available from: https://doi.org/10.7759/cureus.69704
11. National Pharmaceutical Regulatory Agency (NPRA). The Malaysian National ADR Database (QUEST) [Internet]. 2026 [cited 2026 Feb 19]. Available from: https://www.npra.gov.my (access restricted)

 

Written by: Azura Abdullah

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