A signal-detection analysis of the FDA Adverse Event Reporting System reports that all nine marketed glucagon-like peptide-1 receptor agonist products met conventional criteria for a disproportionate reporting signal for impaired gastric emptying. The authors state the analysis is descriptive and hypothesis-generating and makes no claim about clinical risk.

The products covered include semaglutide (sold as Ozempic, Rybelsus and Wegovy), tirzepatide (Mounjaro and Zepbound), dulaglutide (Trulicity), liraglutide (Victoza and Saxenda) and exenatide (Byetta). The authors note that GLP-1 receptor agonists delay gastric emptying as an on-target pharmacological effect, meaning slowed stomach emptying is an expected action of the drug class rather than an unexpected one.

Study overview

The researchers queried the public openFDA interface to FAERS for the nine products, using the MedDRA preferred term "impaired gastric emptying" as the outcome. For each product they calculated the proportional reporting ratio, the reporting odds ratio with 95 percent confidence intervals, and a Yates-corrected chi-square against all other drugs in the database.

Key results

All nine products met the conventional signal thresholds of a proportional reporting ratio of at least 2, a chi-square of at least 4, and at least three reports. Semaglutide-based products showed the strongest disproportionality, with Ozempic at a PRR of 109.1 and Rybelsus at 66.4, followed by Trulicity at 38.5, Wegovy at 31.5 and Mounjaro at 29.5.

Liraglutide products fell lower, at 22.3 for Victoza and 19.3 for Saxenda, with the lowest values reported for Zepbound and Byetta, both at 4.5. The authors write that the contrast between diabetes-indicated and obesity-indicated products containing the same molecule is consistent with confounding by indication rather than a molecule-specific effect.

Limitations

The authors state plainly that disproportionality measures quantify reporting patterns, not incidence or risk, and cannot establish causality. FAERS is a spontaneous reporting database, and counts reflect the full database snapshot at the extraction date.

The work is posted as a preprint and reproduces observations previously reported by independent groups rather than testing them in a new population. The authors say confirmation is required in controlled cohort studies.

What it means

The analysis reproduces a class-wide reporting signal using a method the authors describe as fully transparent and reproducible from public data. What remains unsettled is whether the reporting pattern corresponds to any difference in actual clinical risk between products.