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
Semaglutide-based products show the highest reporting ratios for impaired gastric emptying among GLP-1 receptor agonists, but further studies are needed to understand the clinical significance.
Where it sits
this study against the rest of the semaglutide corpusSummary and findings
This study analyzed the reporting of impaired gastric emptying associated with nine glucagon-like peptide-1 receptor agonists (GLP-1 RAs) using the FDA Adverse Event Reporting System. Semaglutide-based products exhibited the highest disproportionate reporting ratios. The findings indicate a need for further investigation into the clinical implications of these observations.
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 concern of impaired gastric emptying as a potential adverse event associated with GLP-1 receptor agonists, a class of medications used in diabetes management. Understanding the frequency and pattern of such adverse events is crucial for evaluating the safety profile of these medications. Prior to this study, there was limited comprehensive analysis of adverse event reporting across multiple GLP-1 receptor agonists.
Methods
The study employed a signal-detection analysis using data from the FDA Adverse Event Reporting System. It focused on nine GLP-1 receptor agonist products, including semaglutide. Specific details on the methodology, such as sample size, duration, and statistical techniques, were not reported in the title.
Results
Not reported in abstract.
Interpretation
Without detailed results, it is challenging to compare this study's findings to existing literature or assess the clinical significance of the reported adverse events. The reliance on adverse event reporting systems introduces potential biases and limits the ability to draw causal inferences. This study may highlight safety signals that warrant further investigation in controlled settings.
Key findings
- Not reported in abstract.
Limitations
- Not reported in abstract.
- Reliance on adverse event reporting data.
- Potential for reporting bias.
- Lack of controlled experimental conditions.