Serious acute biliary reporting with glucagon-like peptide-1-based therapies versus sodium-glucose cotransporter-2 inhibitors in type 2 diabetes

<jats:p>&lt;b&gt;Aim: &lt;/b&gt;To compare reporting of serious acute biliary events for glucagon-like peptide-1-based therapies, including tirzepatide, with sodium-glucose cotransporter-2 inhibitors among spontaneous reports explicitly linked to type 2 diabetes, while accounting for calendar time and evaluating the stability of any reporting disparity. &lt;b&gt;Methods: &lt;/b&gt;Official United States Food and Drug Administration quarterly extracts for 2013 Q2-2026 Q1 were harmonized and deduplicated. Eligible reports required an exact drug-indication link, primary-suspect role, adult or age-missing status, and receipt after product approval. The composite comprised cholecystitis, acute cholecystitis, biliary colic, bile-duct stone or cholangitis with a serious report outcome. The primary estimate was a calendar-quarter-stratified Mantel-Haenszel reporting odds ratio. &lt;b&gt;Results: &lt;/b&gt;Among 114,102 eligible reports, 84,901 involved glucagon-like peptide-1-based therapies and 29,201 involved sodium-glucose cotransporter-2 inhibitors; 482 met the composite definition. The primary reporting odds ratio was 1.36 (95% confidence interval 1.06-1.75; P = 0.013), with temporal heterogeneity (P = 0.0068). Results were 1.57 (1.23-2.01) when secondary-suspect roles were added and 0.76 (0.47-1.23) during each agent's first four post-launch years. In a post hoc decomposition, estimates were 1.10 (0.84-1.43) through 2024 Q4 and 4.60 (1.89-11.16) in 2025 Q1-2026 Q1. &lt;b&gt;Conclusion: &lt;/b&gt;A modest pooled reporting disparity was concentrated in the latest five quarters rather than being stable across the archive. The finding may reflect changing utilization, reporter composition and stimulated reporting; it does not estimate incidence or establish causality.</jats:p>