Highlights
- The OCULUS randomized clinical trial found that continuing GLP-1/GIP agonists resulted in a 25.0% incidence of clinically significant residual gastric volume (RGV), compared to only 3.1% in the group that held one dose.
- The trial was terminated early by the data safety monitoring board because the risk in the continuation group exceeded
**Structuring the Content**I’m now generating the final content sections, focusing on the background, methods, results, and expert commentary. Expanding on the pharmacology, risks, and statistical methodology is underway. I’m incorporating the key findings and subgroup analysis. I’m verifying the references, ensuring all formatting meets requirements. I’m validating against the JSON schema, and I’m polishing the final structure.
the pre-established O’Brien-Fleming stopping boundary. - Subgroup analysis revealed that patients undergoing combined EGD and colonoscopy—who followed a clear liquid diet the day prior—had no clinically significant RGV, regardless of whether they held their medication.
- These findings suggest that holding one dose of weekly or daily GLP-1/GIP agonists is a critical safety measure to prevent aspiration and procedural complications.
Background: The Challenge of GLP-1 Agonists in Procedural Care
The rapid rise in the use of glucagon-like peptide-1 (GLP-1) receptor agonists and glucose-dependent insulinotropic polypeptide (GIP) agonists has revolutionized the management of type 2 diabetes and obesity. Medications such as semaglutide and tirzepatide are now among the most frequently prescribed drugs globally. However, their primary mechanism of action—slowing gastric emptying to promote satiety and glycemic control—presents a unique challenge in the perioperative setting.
For patients undergoing endoscopic procedures or surgery under sedation, the presence of residual gastric volume (RGV) poses a significant risk of pulmonary aspiration, a potentially life-threatening complication. Until recently, clinical guidelines regarding the management of these medications prior to elective procedures were based largely on expert consensus rather than high-quality randomized data. The American Society of Anesthesiologists (ASA) previously suggested holding these medications, but the lack of definitive evidence led to inconsistent practices across health systems. The OCULUS (Optimal Control of GLP-1/GIP Agonists in Upper Endoscopy) trial was designed to fill this critical evidence gap.
The OCULUS Study: Design and Methodology
Participants and Setting
This randomized, single-masked clinical trial was conducted at two large tertiary referral centers in the United States between July 2024 and May 2025. The study enrolled 60 adult patients who were on a stable dose of a GLP-1 or GLP-1/GIP agonist for at least one month and were scheduled for elective upper endoscopy (EGD), either alone or in combination with a colonoscopy. Participants were excluded if they had a history of foregut surgery, achalasia, documented gastroparesis, or recent opioid use—all factors that could independently influence gastric motility.
Intervention and Primary Outcome
Patients were randomized into two groups: the “hold” group, which omitted one dose of their medication (weekly or daily) prior to the procedure, and the “continue” group, which maintained their regular dosing schedule. The primary outcome was clinically significant residual gastric volume (RGV). This was defined as a composite of gastric contents that: (1) precluded a thorough endoscopic examination, (2) required the premature termination of the procedure or emergency endotracheal intubation, or (3) resulted in an aspiration event necessitating extended monitoring or hospital admission.
Key Findings: A Stark Contrast in Gastric Volume
The results of the interim analysis were so definitive that the trial was halted early for safety. Among the 60 patients analyzed, clinically significant RGV occurred in 25.0% of the continuation group compared to only 3.1% in the hold group. This represents an absolute risk difference of 21.9% (90% CI, 7.0%-36.7%; P = .003).
Subgroup Analysis: EGD vs. EGD Plus Colonoscopy
The study provided even more granular insights when looking at the specific type of procedure. In the subgroup of 35 patients undergoing EGD only, the disparity was even more pronounced: 46.7% of those who continued their medication had clinically significant RGV, compared to 5.0% in the hold group (absolute difference 41.7%; P = .001).
Intriguingly, the 25 patients who underwent both EGD and colonoscopy showed no instances of clinically significant RGV in either the hold or continue groups. This suggests that the clear liquid diet required for colonoscopy preparation effectively mitigates the delayed gastric emptying effects of GLP-1/GIP agonists, ensuring the stomach is sufficiently empty despite the pharmacological slowing of motility.
Expert Commentary: Mechanistic Insights and Clinical Implications
The OCULUS trial provides the most robust evidence to date that GLP-1 and GIP agonists significantly alter the reliability of standard fasting protocols. The pharmacodynamics of these agents involve a reduction in the rate of gastric phase 3 contractions and a delay in the emptying of solids and liquids. While this is beneficial for postprandial glucose regulation, it creates a “full stomach” scenario even after traditional fasting periods.
Medical experts note that the study’s finding regarding the clear liquid diet is particularly actionable. For patients who are at high risk of glycemic instability if they hold their medication, or for those who mistakenly take their dose, switching to a clear liquid diet for 24 hours prior to the procedure may serve as a viable alternative to cancellation. However, for most elective EGD cases, holding the dose remains the safest and most straightforward approach.
Safety and Limitations
While the study clearly showed an increase in RGV, it did not find a statistically significant increase in actual aspiration events or other adverse outcomes in this small cohort. However, the presence of RGV is a well-established surrogate for aspiration risk. The early termination of the trial, while ethically necessary, limits the total sample size, though the statistical significance of the primary endpoint remained robust. It is also important to note that the study focused on stable doses; patients in the titration phase of these medications might experience even more unpredictable gastric emptying patterns.
Conclusion: Shaping Future Perioperative Guidelines
The OCULUS trial provides clear, randomized evidence that holding one dose of a GLP-1 or GIP agonist before upper endoscopy significantly reduces the risk of clinically significant residual gastric volume. For clinicians, these findings reinforce the importance of thorough pre-procedural screening and patient education. In cases where the medication cannot be held, or as an added layer of safety, a 24-hour clear liquid diet appears to be an effective mitigation strategy.
As these medications continue to proliferate in the patient population, the OCULUS trial will likely serve as a cornerstone for updated perioperative and periprocedural guidelines, ensuring that the benefits of GLP-1 therapies do not come at the expense of procedural safety.
Funding and Trial Registration
This study was supported by institutional clinical research funds. The trial is registered at ClinicalTrials.gov with the identifier NCT06533527.
References
1. Ahmad AI, Garg S, Jacobs J, et al. Holding vs Continuing GLP-1/GIP Agonists Before Upper Endoscopy: The OCULUS Randomized Clinical Trial. JAMA Intern Med. 2026-03-16. PMID: 41837981.
2. American Society of Anesthesiologists. Practice Guidelines for Preoperative Fasting and the Use of Pharmacologic Agents to Reduce the Risk of Pulmonary Aspiration. Anesthesiology. 2023.
3. Drucker DJ. Mechanisms of Action of GLP-1 Receptor Agonists and GIP Receptor Agonists. Diabetes Care. 2018;41(12):2626-2635.