Safety analysis of compounded GLP-1 receptor agonists: a pharmacovigilance study using the FDA adverse event reporting system.
Level 4 - case-series / case-control
Retrospective pharmacovigilance disproportionality analysis of spontaneous adverse event reports (FAERS)
PubMed 40285721 · doi:10.1080/14740338.2025.2499670
What was done
Researchers conducted a retrospective pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database from 2018 to 2024. They compared adverse event reports, medication errors, and product quality issues for compounded versus non-compounded formulations of liraglutide, semaglutide, and tirzepatide. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated using adjusted logistic regression.
What was found
Of 81,078 GLP-1 receptor agonist reports identified, 707 involved compounded products. Compounded formulations demonstrated significantly higher reporting odds for abdominal pain (ROR 2.84 [95% CI 2.29, 3.49]), diarrhea (1.59 [1.25, 1.99]), nausea (1.27 [1.05, 1.52]), suicidality (6.34 [4.32, 8.99]), cholecystitis (3.39 [1.61, 6.31]), and hospitalization (2.35 [1.94, 2.83]). Compounded products also showed higher reporting odds for preparation errors (48.92 [12.63, 189.6]), prescribing errors (4.46 [2.49, 7.98]), contamination (19.00 [4.24, 85.03]), and compounding/manufacturing issues (8.51 [5.17, 14.0]), but lower reporting odds of administration errors (0.29 [0.16, 0.53]) and dosing errors (0.24 [0.17, 0.32]).
Why it matters
As demand and shortages drive the use of compounded alternatives to brand-name GLP-1 receptor agonists, this study provides pharmacovigilance signals linking compounded products to higher odds of adverse events, contamination, preparation errors, and hospitalizations.
Limits
The study is based on FAERS, a passive surveillance database subject to voluntary reporting, underreporting, reporting bias, and inconsistent data quality. Total patient exposure is unknown, precluding incidence calculation, and disproportionality metrics cannot establish direct causality.
Cited by
- supports Under US regulatory rules during an official drug shortage, compounding pharmacies are permitted to manufacture compounded versions of medications to meet the shortage.