Substance-Level Disproportionate Reporting of Impaired Gastric Emptying for Five Glucagon-Like Peptide-1 Receptor Agonists: A Reproducible Signal-Detection Analysis of the FDA Adverse Event Reporting System
Exenatide shows a lower disproportionality in impaired gastric emptying reports compared to other GLP-1 RAs, but the findings are descriptive and not indicative of clinical risk.
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 disproportionate reporting of impaired gastric emptying for five GLP-1 receptor agonists, including exenatide. Exenatide showed a proportional reporting ratio of 4.7, indicating a lower disproportionality compared to other substances. The analysis is descriptive and does not establish causality.
Abstract
<title>Abstract</title> <p>Background. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) delay gastric emptying as an on-target effect. Independent FAERS analyses have reported that GLP-1 RAs account for a large share of impaired-gastric-emptying (IGE) reports (Huang et al., 2025; Tu et al., 2026). We sought to reproduce this signal at the active-substance level using a transparent, fully reproducible pipeline, without asserting causation. Methods. Using the public openFDA interface to the FDA Adverse Event Reporting System (FAERS), we identified reports for five GLP-1 RA substances via the generic-name field. The outcome was the MedDRA Preferred Term "Impaired gastric emptying" (10021518). For each substance we computed the proportional reporting ratio (PRR), reporting odds ratio (ROR), 95% confidence intervals, and the Yates-corrected chi-square. Counts reflect the full database snapshot at the extraction date; all figures are reproducible from the public openFDA source using the analysis script. Results. All five substances met conventional signal criteria. Semaglutide showed the strongest disproportionality (PRR 88.7, 95% CI 85.1–92.4; 3,052 of 82,911 reports), followed by dulaglutide (37.7; 1,593/86,770), liraglutide (20.9; 563/50,219), tirzepatide (20.2; 1,409/140,435), and exenatide (4.7; 136/52,308). Conclusions. These results reproduce, with a transparent and fully reproducible method, the substance-level IGE disproportionate-reporting signal described by independent groups. Disproportionality quantifies reporting, not incidence or risk, and cannot establish causality. The analysis is descriptive and hypothesis-generating and makes no claim about clinical risk.</p>
Background
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known to delay gastric emptying as an on-target effect. Previous analyses of the FDA Adverse Event Reporting System (FAERS) have suggested that GLP-1 RAs are frequently reported in cases of impaired gastric emptying. This study aims to reproduce these findings at the substance level using a reproducible analysis pipeline.
Methods
The study utilized the public openFDA interface to access the FDA Adverse Event Reporting System (FAERS) data. Reports for five GLP-1 RA substances were identified using the generic-name field. The primary outcome was the MedDRA Preferred Term 'Impaired gastric emptying' (10021518). The analysis calculated proportional reporting ratios (PRR), reporting odds ratios (ROR), 95% confidence intervals, and the Yates-corrected chi-square for each substance.
Results
All five substances met conventional signal criteria for disproportionality. Semaglutide showed the highest disproportionality with a PRR of 88.7 (95% CI 85.1–92.4), followed by dulaglutide, liraglutide, tirzepatide, and exenatide, which had a PRR of 4.7. These findings indicate varying levels of disproportionate reporting of impaired gastric emptying among the substances.
Interpretation
The study reproduces previous findings of disproportionate reporting of impaired gastric emptying for GLP-1 RAs using a transparent method. However, the analysis is descriptive and does not imply clinical risk or causality. The lower PRR for exenatide suggests it may have a lesser association with impaired gastric emptying compared to other GLP-1 RAs, but this remains hypothesis-generating.
Key findings
- Semaglutide PRR 88.7, 95% CI 85.1–92.4; 3,052 of 82,911 reports
- Dulaglutide PRR 37.7; 1,593/86,770
- Liraglutide PRR 20.9; 563/50,219
- Tirzepatide PRR 20.2; 1,409/140,435
- Exenatide PRR 4.7; 136/52,308
Limitations
- Descriptive analysis only
- Cannot establish causality
- Disproportionality quantifies reporting, not incidence or risk