Do incretin drugs flag biliary harm in FAERS?

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Among 2,215 biliary FAERS reports, DPP-4 inhibitors had ROR 3.09 (sitagliptin 3.46); overall GLP-1 RAs were called non-significant (ROR 1.60) but semaglutide (4.06) and liraglutide (3.88) signaled.

Source

Association between GLP-1 RAs and DPP-4 inhibitors with biliary disorders: pharmacovigilance analysis

He L, Li J, Cheng X, et al. · Frontiers in pharmacology · 2025

doi.org/10.3389/fphar.2025.1509561 Read the full paper ↗6 citationscc by

Study at a glance

Design: Other — FAERS/OpenVigil 2.1 disproportionality (ROR, PRR, BCPNN, EBGM) of GLP-1 RAs and DPP-4 inhibitors vs biliary SMQs, Q1 2013–Q1 2024
N: N=2215 · 2,215 biliary adverse-event reports (1,709 GLP-1 RA; 506 DPP-4 inhibitor) with the drug as primary suspect
Population: Spontaneous FAERS reports for six GLP-1 RAs and four DPP-4 inhibitors, 2013 Q1–2024 Q1
Outcome: Reporting odds ratios and serious-outcome fractions for biliary SMQ subgroups including gallstones and biliary malignancy

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What they did

Pulled OpenVigil/FAERS primary-suspect reports for GLP-1 RAs and DPP-4 inhibitors (Q1 2013–Q1 2024), mapped biliary SMQs, and ran ROR, PRR, BCPNN, and EBGM disproportionality plus serious-outcome counts.

What they found

2,215 biliary AEs (1,709 GLP-1 RA; 506 DPP-4). DPP-4 class ROR 3.09; sitagliptin 3.46. GLP-1 class ROR 1.60 was labeled not significant, but semaglutide and liraglutide signaled. Serious outcomes: 76.88% of DPP-4 vs 51.55% of GLP-1 reports.

The limits

What it doesn't show

FAERS cannot prove incidence or causality; stimulated reporting, confounding by indication, and missing denominators bias RORs, and “not significant” for GLP-1 overall used a stricter signal rule than CI excluding 1.

Key terms

FAERS: FDA Adverse Event Reporting System of spontaneous safety reports.
ROR: Reporting odds ratio comparing the drug vs other drugs for an event.
GLP-1 RA: Glucagon-like peptide-1 receptor agonist (e.g. semaglutide, liraglutide).
DPP-4 inhibitor: Dipeptidyl peptidase-4 inhibitor (e.g. sitagliptin) that prolongs endogenous GLP-1.
SMQ: Standardised MedDRA query grouping related adverse-event terms.
Primary suspect: Drug coded as the main suspected cause on the FAERS case.

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This analysis used:

Common questions

How many biliary reports?

2,215 (1,709 GLP-1 RA; 506 DPP-4).

DPP-4 class ROR?

3.09 (2.83–3.37).

Which GLP-1 drugs signaled?

Semaglutide ROR 4.06 and liraglutide 3.88.

Serious outcomes more common with which class?

DPP-4 inhibitors (76.88% vs 51.55%).