Adverse events administering glucagon-like peptide-1 receptor agonists: a cross-sectional study.

This cross-sectional study analyzed publicly available FDA Adverse Event Reporting System (FAERS) data from January 2015 through December 2024 to characterize adverse events (AEs) associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs), using injectable insulin as a comparator. Across 112,532 reports where a GLP-1 RA was the primary suspect drug, the study found that administration-related reactions accounted for 63% of GLP-1 RA reports versus 39% for insulin. Reports of dosing issues and administration errors for GLP-1 RAs rose notably beginning in Q4 2022 and continued increasing through 2023 and 2024 — a pattern not observed for insulin — temporally coinciding with documented national GLP-1 supply shortages. The authors note several important limitations: FAERS data lack exposure denominators, making it impossible to calculate true incidence rates; reporting volume increases may reflect greater overall utilization rather than elevated per-patient risk; and FAERS is subject to underreporting and reporting biases. The study concludes that these patterns highlight the need for enhanced patient and provider education and continued post-marketing surveillance, particularly as compounded or alternative GLP-1 formulations may have contributed to administration errors during the shortage period.

Why this grade: While the study uses a large real-world human database (n=112,532 reports), it is a cross-sectional passive surveillance analysis of spontaneous AE reports that lacks exposure denominators, a control group, and causal inference capability, limiting the strength of conclusions drawn.