Serious acute biliary reporting with glucagon-like peptide-1-based therapies versus sodium-glucose cotransporter-2 inhibitors in type 2 diabetes
There is a reported odds ratio of 1.36 for serious acute biliary events with glucagon-like peptide-1 therapies compared to sodium-glucose cotransporter-2 inhibitors, but this does not establish causality or incidence.
Where it sits
this study against the rest of the tirzepatide corpusSummary and findings
This study compared the reporting of serious acute biliary events associated with glucagon-like peptide-1-based therapies, including tirzepatide, to sodium-glucose cotransporter-2 inhibitors in type 2 diabetes. The analysis included 114,102 eligible reports from 2013 Q2 to 2026 Q1. A primary reporting odds ratio of 1.36 was observed.
Abstract
<b>Aim: </b>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. <b>Methods: </b>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. <b>Results: </b>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. <b>Conclusion: </b>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.
Background
The paper addresses the safety profile of GLP-1-based therapies, particularly concerning serious acute biliary events, in the context of type 2 diabetes management. Previous studies have indicated potential risks associated with GLP-1 therapies, but comparative data with SGLT-2 inhibitors remain limited. This study aims to fill that gap by providing insights into the incidence of these events.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Not reported in abstract.
Key findings
- Not reported in abstract.
Limitations
- Not reported in abstract.