Acute pancreatitis with incretin-based therapies
Do incretin-based therapies increase the incidence of acute pancreatitis?
§1Abstract
§1.1Review question
Do incretin-based therapies increase the incidence of acute pancreatitis?
§1.2PICO frame
Table 1. The registered PICO frame. Any change made after protocol registration is recorded in the amendment log at §5 and is identified there as post hoc.
| Element | As registered |
|---|---|
| Population | Adults exposed to an incretin-based therapy in a randomised trial or a controlled observational study. |
| Intervention | Any incretin receptor agonist. |
| Comparator | Placebo or an active comparator. |
| Outcomes | Adjudicated acute pancreatitis; pancreatic enzyme elevation; pancreatic cancer. |
§1.3Method in brief
A review of harms, in which the absence of an event in a trial of conventional size is treated as uninformative rather than as reassurance. The protocol was registered with the Institute's secretariat before the search was executed. The search was run on 4 September 2025 across 8 sources and is reproduced in full at §2. Screening, extraction and certainty assessment were performed independently by two members of the secretariat with disagreement resolved by a third.[1]
§1.4Conclusion
Moderate certainty evidence from the pooled cardiovascular outcome trials, in which pancreatitis was adjudicated and exposure was long, does not indicate a materially increased incidence. Observational analyses have reported associations of varying magnitude and are subject to confounding by indication and by the shared risk factors of obesity and gallstone disease. The Institute records that the trial evidence is more informative than the observational evidence for this question because the exposure is randomised, and that the trials were not powered for it.
The conclusion rests on 24 contributing studies, listed with their extracted data at §3 and summarised outcome by outcome at §4.
§1.5Limitations
§1.6Consultation
This review was released for public comment before ratification. Draft synthesis: Acute pancreatitis with incretin-based therapies received 10 submissions. Amendments arising are recorded in the amendment log and are traceable to a numbered submission.
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Sodhi M, Rezaeianzadeh R, Kezouh A, Etminan M. Risk of gastrointestinal adverse events associated with glucagon-like peptide-1 receptor agonists for weight loss. JAMA 2023;330(18):1795–1797. doi:10.1001/jama.2023.19574 · PMID 37796527
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.