GLP-1 Agonists Before Endoscopy (OCULUS Trial): JAMA | April 2026

Introduction

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonists have rapidly become integral in the management of type 2 diabetes, obesity, and metabolic diseases due to their effects on glycemic control and weight loss. A key mechanism underlying their efficacy is delayed gastric emptying, which raises concerns in procedural settings such as upper endoscopy, where retained gastric contents may increase the risk of aspiration. Despite widespread adoption of precautionary guidelines recommending withholding these agents before procedures, robust prospective evidence has been lacking.

Problem Statement

Current clinical practice is largely guided by expert opinion and limited retrospective data, leading to variability in recommendations regarding whether GLP-1/GIP agonists should be withheld before endoscopy. This uncertainty has practical implications, including procedure delays, cancellations, and potential compromise of metabolic control, highlighting the need for high-quality randomized evidence.

Summary

The OCULUS randomised clinical trial demonstrated that continuing GLP-1/GIP agonists significantly increased clinically relevant residual gastric volume compared to holding one dose before endoscopy (25% vs 3.1%). However, importantly, this did not translate into an increased rate of aspiration-related adverse events. Notably, patients undergoing combined procedures with a prior clear liquid diet showed negligible risk, suggesting a potential mitigating strategy.

Overall, the study provides the first high-quality evidence supporting a balanced, individualised approach, where holding medication reduces gastric residue, but continuation may still be safe in selected settings, particularly with appropriate dietary preparation.