Comprehensive pharmacovigilance assessment of pairwise drug-drug interactions and acute pancreatitis in the FDA adverse event reporting system: focus on incretin-based drugs.

Kazume I, Onda K, Tanaka S, Yokokawa T, Suzuki K

Frontiers in drug safety and regulation10 Jun 2026

PMID42359103PMCIDPMC13291152DOI10.3389/fdsfr.2026.1827098PepBankPUB-42359103

Summary

BackgroundDrug-induced pancreatitis remains a clinically important condition owing to its severity and relevance to pharmacotherapeutic risk management. Incretin-based antidiabetic agents, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, are associated with an increased risk of acute pancreatitis (AP). However, the extent to which concomitant medication modifies AP has not yet been systematically elucidated. We conducted a comprehensive systematic drug-drug interaction (DDI) assessment involving GLP-1 RA and DPP-4 inhibitors using the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS).MethodsDisproportionality analyses were conducted using the FAERS data (JAPIC FAERS) from the fourth quarter of 1997 to the first quarter of 2024. Crude reporting odds ratios (cRORs) were calculated to assess the association between individual drugs and AP. DDI signals for 1:1 concomitant use involving GLP-1 RAs or DPP-4 inhibitors were comprehensively evaluated using the Ω shrinkage measure, with Ω₀₂₅ as the signal detection criterion. Ω₀₂₅ were analyzed for all pooled cases, and temporal trends were assessed across six multi-year periods using a period-stratified analysis.ResultsElevated cRORs for AP were observed for several agents, including GLP-1 RAs, DPP-4 inhibitors, and other antidiabetic medications. Pairwise DDI analyses of GLP-1 RAs or DPP-4 inhibitors with other drugs identified positive interaction signals in 308 drug pairs in pooled analyses. Period-stratified analyses narrowed the findings to 11 drug pairs with consistent signals across ≥3 of 6 periods, including dulaglutide-atorvastatin (four periods). However, no concomitant drug combinations involving GLP-1 RAs or DPP-4 inhibitors were identified as being robustly associated with increased AP reporting.ConclusionPeriod-stratified analysis helped mitigate false-positive signals identified in the pooled DDI analyses. Drug pairs exhibiting recurrent weak AP signals warrant continued pharmacovigilance and further evaluation.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone2

In this study, Dulaglutide (Trulicity) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Dulaglutide (Trulicity).

01HumanNot a test of Dulaglutide (Trulicity) aloneObservational studySafety outcome
In FAERS database analysis, dulaglutide with atorvastatin showed positive acute pancreatitis interaction signals in four periods.
In plain wordsDatabase analysis found pancreatitis reporting interaction signals for dulaglutide with atorvastatin in four periods.
Peptide
Dulaglutide (Trulicity)
Outcome
Direction not reportedAcute pancreatitis reporting
Study
Homo sapiensn: not reported in source
Individual adverse event reports in the FDA Adverse Event Reporting System
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Measurements
Periods with consistent interaction signal
4 periods
dulaglutide-atorvastatin pair, period-stratified analysis of 6 periods
Source sentences
Summary
Period-stratified analyses narrowed the findings to 11 drug pairs with consistent signals across ≥3 of 6 periods, including dulaglutide-atorvastatin (four periods).
2 context sentences(design, population, supporting numbers)
Summary · context
Disproportionality analyses were conducted using the FAERS data (JAPIC FAERS) from the fourth quarter of 1997 to the first quarter of 2024.
Summary · context
DDI signals for 1:1 concomitant use involving GLP-1 RAs or DPP-4 inhibitors were comprehensively evaluated using the Ω shrinkage measure, with Ω₀₂₅ as the signal detection criterion.
In this study, Dulaglutide (Trulicity) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Dulaglutide (Trulicity).
Show in the study text Report a problemFND-4235910301
02HumanNot a test of Dulaglutide (Trulicity) aloneObservational studySafety outcome
In FAERS database analysis, no incretin drug combinations, including dulaglutide combinations, showed robust associations with increased acute pancreatitis reporting.
In plain wordsDatabase analysis found no robust increased pancreatitis reporting association for incretin drug combinations, including dulaglutide combinations.
Peptide
Dulaglutide (Trulicity)
Outcome
Direction not reportedAcute pancreatitis reporting
Study
Homo sapiensn: not reported in source
Individual adverse event reports in the FDA Adverse Event Reporting System
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
However, no concomitant drug combinations involving GLP-1 RAs or DPP-4 inhibitors were identified as being robustly associated with increased AP reporting.
2 context sentences(design, population, supporting numbers)
Summary · context
Disproportionality analyses were conducted using the FAERS data (JAPIC FAERS) from the fourth quarter of 1997 to the first quarter of 2024.
Summary · context
DDI signals for 1:1 concomitant use involving GLP-1 RAs or DPP-4 inhibitors were comprehensively evaluated using the Ω shrinkage measure, with Ω₀₂₅ as the signal detection criterion.
In this study, Dulaglutide (Trulicity) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Dulaglutide (Trulicity).
Show in the study text Report a problemFND-4235910302

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Version 2Current
22 Oct 2026, 02:25 UTC
Study results updated
Version 1
21 Oct 2026, 18:59 UTC
First added · source update from Europe PMC

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