##common.pageHeaderLogo.altText##

Viewpoint

Vol. 155 No. 10 (2025)

Is GLP-1 receptor agonist therapy safe for patients with intraductal papillary mucinous neoplasm?

Cite this as:
Swiss Med Wkly. 2025;155:4850
Published
15.10.2025

Summary

Glucagon-like peptide-1 receptor agonists are increasingly used in the management of obesity and diabetes. Their potential risks, however, particularly regarding pancreatitis and pancreatic cancer, remain contentious. Despite numerous studies and meta-analyses indicating no significant correlation between GLP-1 RA therapy and the incidence of acute pancreatitis or pancreatic cancer, gaps in the literature persist regarding their effects in patients with frequent pancreatic conditions, such as intraductal papillary mucinous neoplasms, a disease with potential for malignant transformation. Further rigorous clinical studies addressing the safety of GLP-1 receptor agonists in patients with intraductal papillary mucinous neoplasms should be conducted to understand the potential risks and benefits, establish clear guidelines for clinical practice and ultimately ensure the safety of these medications in this potentially vulnerable patient population.

References

  1. 1.Masson W, Lobo M, Barbagelata L, Lavalle-Cobo A, Nogueira JP. Acute pancreatitis due to different semaglutide regimens: an updated meta-analysis. Endocrinol Diabetes Nutr (Engl Ed). 2024 Mar;71(3):124–32. 10.1016/j.endien.2024.03.012
  2. 2.Tan HC, Dampil OA, Marquez MM. Efficacy and Safety of Semaglutide for Weight Loss in Obesity Without Diabetes: A Systematic Review and Meta-Analysis. J ASEAN Fed Endocr Soc. 2022;37(2):65–72. 10.15605/jafes.037.02.14
  3. 3. Pinto LC, Falcetta MR, Rados DV et al. Glucagon-like peptide-1 receptor agonists and pancreatic cancer: a meta-analysis with trial sequential analysis. Sci Rep. 2019;9(1):2375. Published 2019 Feb 20. doi:10.1038/s41598-019-38956-2
  4. 4.Lomeli LD, Kodali AM, Tsushima Y, Mehta AE, Pantalone KM. The incidence of acute pancreatitis with GLP-1 receptor agonist therapy in individuals with a known history of pancreatitis. Diabetes Res Clin Pract. 2024 Sep;215:111806. 10.1016/j.diabres.2024.111806
  5. 5.Nreu B, Dicembrini I, Tinti F, Mannucci E, Monami M. Pancreatitis and pancreatic cancer in patients with type 2 diabetes treated with glucagon-like peptide-1 receptor agonists: an updated meta-analysis of randomized controlled trials. Minerva Endocrinol (Torino). 2023 Jun;48(2):206–13. 10.23736/S2724-6507.20.03219-8
  6. 6.Rouse R, Xu L, Stewart S, Zhang J. High fat diet and GLP-1 drugs induce pancreatic injury in mice. Toxicol Appl Pharmacol. 2014 Apr;276(2):104–14. 10.1016/j.taap.2014.01.021
  7. 7.Nachnani JS, Bulchandani DG, Nookala A, Herndon B, Molteni A, Pandya P, et al. Biochemical and histological effects of exendin-4 (exenatide) on the rat pancreas. Diabetologia. 2010 Jan;53(1):153–9. 10.1007/s00125-009-1515-4
  8. 8.Deng H, Yang F, Ma X, Wang Y, Chen Q, Yuan L. Long-Term Liraglutide Administration Induces Pancreas Neogenesis in Adult T2DM Mice. Cell Transplant. 2020;29:963689720927392. 10.1177/0963689720927392
  9. 9.Gier B, Matveyenko AV, Kirakossian D, Dawson D, Dry SM, Butler PC. Chronic GLP-1 receptor activation by exendin-4 induces expansion of pancreatic duct glands in rats and accelerates formation of dysplastic lesions and chronic pancreatitis in the Kras(G12D) mouse model [published correction appears in Diabetes. 2012 Aug;61(8):2195]. Diabetes. 2012 May;61(5):1250–62. 10.2337/db11-1109
  10. 10.Tatarkiewicz K, Smith PA, Sablan EJ, Polizzi CJ, Aumann DE, Villescaz C, et al. Exenatide does not evoke pancreatitis and attenuates chemically induced pancreatitis in normal and diabetic rodents. Am J Physiol Endocrinol Metab. 2010 Dec;299(6):E1076–86. 10.1152/ajpendo.00479.2010
  11. 11.Nyborg NC, Mølck AM, Madsen LW, Knudsen LB. The human GLP-1 analog liraglutide and the pancreas: evidence for the absence of structural pancreatic changes in three species. Diabetes. 2012 May;61(5):1243–9. 10.2337/db11-0936
  12. 12.Vahle JL, Byrd RA, Blackbourne JL, Martin JA, Sorden SD, Ryan T, et al. Effects of the GLP-1 Receptor Agonist Dulaglutide on the Structure of the Exocrine Pancreas of Cynomolgus Monkeys. Toxicol Pathol. 2015 Oct;43(7):1004–14. 10.1177/0192623315588999
  13. 13.Klibansky DA, Reid-Lombardo KM, Gordon SR, Gardner TB. The clinical relevance of the increasing incidence of intraductal papillary mucinous neoplasm. Clin Gastroenterol Hepatol. 2012 May;10(5):555–8. 10.1016/j.cgh.2011.12.029
  14. 14.Capurso G, Boccia S, Salvia R, Del Chiaro M, Frulloni L, Arcidiacono PG, et al.; Italian Association for Study of Pancreas (AISP); Intraductal Papillary Mucinous Neoplasm (IPMN) Study Group. Risk factors for intraductal papillary mucinous neoplasm (IPMN) of the pancreas: a multicentre case-control study. Am J Gastroenterol. 2013 Jun;108(6):1003–9. 10.1038/ajg.2013.42
  15. 15.Aronsson L, Andersson R, Ansari D. Intraductal papillary mucinous neoplasm of the pancreas - epidemiology, risk factors, diagnosis, and management. Scand J Gastroenterol. 2017 Aug;52(8):803–15. 10.1080/00365521.2017.1318948
  16. 16. Xu JH, Ni CY, Zhuang YY, et al. Acute pancreatitis in intraductal papillary mucinous neoplasm: a single-center retrospective cohort study with systematic review and meta-analysis. BMC Gastroenterol. 2023;23(1):424. Published 2023 Dec 1. doi:10.1186/s12876-023-02972-4
  17. 17.Ohtsuka T, Fernandez-Del Castillo C, Furukawa T, Hijioka S, Jang JY, Lennon AM, et al. International evidence-based Kyoto guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas. Pancreatology. 2024 Mar;24(2):255–70. 10.1016/j.pan.2023.12.009
  18. 18.Tanaka M, Fernández-Del Castillo C, Kamisawa T, Jang JY, Levy P, Ohtsuka T, et al. Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology. 2017;17(5):738–53. 10.1016/j.pan.2017.07.007