Class-Wide Disproportionate Reporting of Impaired Gastric Emptying Across Nine Glucagon-Like Peptide-1 Receptor Agonist Products: A Signal-Detection Analysis of the FDA Adverse Event Reporting System
The study identifies a disproportionate reporting signal for impaired gastric emptying across GLP-1 RAs, particularly for semaglutide products, but does not establish causality.
Where it sits
this study against the rest of the exenatide corpusSummary and findings
The study analyzed the FDA Adverse Event Reporting System to assess the reporting of impaired gastric emptying across nine GLP-1 receptor agonists. It found that all products met conventional signal criteria for disproportionate reporting, with semaglutide-based products showing the highest disproportionality. The analysis is descriptive and does not establish causality.
Abstract
<title>Abstract</title> <p> <bold>Background.</bold> Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) delay gastric emptying as an on-target pharmacological effect. Independent pharmacovigilance analyses have reported that GLP-1 RAs account for a large share of impaired-gastric-emptying (IGE) reports in spontaneous databases (Huang et al., 2025; Tu et al., 2026). We sought to reproduce these observations across marketed products using a fully transparent, reproducible pipeline, without asserting causation. <bold>Methods.</bold> We queried the public openFDA interface to the FDA Adverse Event Reporting System (FAERS) for nine GLP-1 RA products. The outcome was the MedDRA Preferred Term "Impaired gastric emptying" (10021518). For each product we computed the proportional reporting ratio (PRR), reporting odds ratio (ROR), 95% confidence intervals, and the Yates-corrected chi-square against all other drugs in the database. Counts reflect the full database snapshot at the extraction date; all reported figures are reproducible from the public openFDA source using the analysis script. <bold>Results.</bold> All nine products met conventional signal criteria (PRR ≥ 2, χ² ≥ 4, N ≥ 3). Semaglutide-based products showed the strongest disproportionality (Ozempic PRR 109.1; Rybelsus 66.4), followed by dulaglutide (Trulicity 38.5), semaglutide for obesity (Wegovy 31.5), tirzepatide for diabetes (Mounjaro 29.5), liraglutide (Victoza 22.3; Saxenda 19.3), and the lowest signals for tirzepatide-obesity (Zepbound 4.5) and exenatide (Byetta 4.5). Full confidence intervals, ROR, and chi-square values are reported in Table 1. The same-molecule contrast between diabetes- and obesity-indicated products is consistent with confounding by indication rather than a molecule-specific effect. <bold>Conclusions.</bold> These results reproduce, with a transparent and fully reproducible method, the class-wide IGE disproportionate-reporting signal previously reported by independent groups. Disproportionality measures quantify reporting patterns, not incidence or risk, and cannot establish causality. The analysis is descriptive and hypothesis-generating; it makes no claim about clinical risk and requires confirmation in controlled cohort studies. </p>
Background
The study addresses the question of whether GLP-1 receptor agonists are disproportionately reported for causing impaired gastric emptying in pharmacovigilance databases. Previous independent analyses have suggested a high share of such reports for GLP-1 RAs. This study aims to reproduce these findings using a transparent and reproducible method, which is important for understanding the safety profile of these drugs.
Methods
The study utilized the public openFDA interface to query the FDA Adverse Event Reporting System for nine GLP-1 RA products. The primary outcome was the MedDRA Preferred Term 'Impaired gastric emptying'. Proportional reporting ratio (PRR), reporting odds ratio (ROR), 95% confidence intervals, and Yates-corrected chi-square were computed for each product. The analysis was based on a full database snapshot at the extraction date.
Results
All nine GLP-1 RA products met the conventional signal criteria for disproportionate reporting of impaired gastric emptying. Semaglutide-based products showed the strongest disproportionality, with Ozempic having a PRR of 109.1 and Rybelsus 66.4. The lowest signals were observed for tirzepatide-obesity (Zepbound) and exenatide (Byetta), both with a PRR of 4.5. The analysis suggests potential confounding by indication rather than a molecule-specific effect.
Interpretation
The study's findings are consistent with previous reports of disproportionate reporting of impaired gastric emptying for GLP-1 RAs. However, the results are descriptive and hypothesis-generating, highlighting the need for controlled cohort studies to confirm any clinical risk. The high PRR values for semaglutide products suggest a strong reporting signal, but this does not imply a higher incidence of adverse events. Confounding by indication may also play a role in the observed patterns.
Key findings
- PRR ≥ 2, χ² ≥ 4, N ≥ 3 for all nine products.
- Ozempic PRR 109.1; Rybelsus 66.4.
- Trulicity PRR 38.5.
- Wegovy PRR 31.5.
- Byetta PRR 4.5.
Limitations
- Descriptive analysis, not causal.
- Based on spontaneous reporting.
- Potential for reporting biases.
- Confounding by indication.