OCULUS Trial: Holding vs Continuing GLP-1/GIP Agonists Before Upper Endoscopy

Key Takeaways

• In adults undergoing elective upper endoscopy, continuation of therapy was associated with more clinically significant residual gastric volume than holding one dose.
• All primary-outcome events occurred in the upper-endoscopy-only subgroup, while none were seen with combined upper endoscopy and colonoscopy after clear liquids the day before.
• No aspiration-related or other immediate escalation events were observed, and symptom screening did not identify most patients with clinically significant residual gastric volume.

Among adults on stable GLP-1 or GLP-1/GIP agonists undergoing elective upper endoscopy, the OCULUS randomized clinical trial in JAMA Internal Medicine compared continuation with holding one dose. Clinically significant residual gastric volume appeared in 25.0% of patients who continued their therapy and 3.1% of the hold group. The comparison was limited to sedated upper endoscopic procedures rather than broader perioperative settings.

Researchers conducted a randomized, single-masked clinical trial at 2 US tertiary referral centers, with endoscopists and anesthesiologists unaware of assignment, at Cleveland Clinic sites in Weston, Florida, and Cleveland, Ohio. Recruitment ran from July 2024 through May 2025, and publication followed online on March 16, 2026. Eligible participants were adults aged 18 years or older on a stable GLP-1 or GLP-1/GIP agonist dose for at least 1 month. They were scheduled for elective EGD, EUS, or ERCP under moderate sedation or monitored anesthesia care, and colonoscopy was allowed only with an upper procedure. Patients were randomized to continue dosing or hold one dose, set at 7 to 13 days for weekly drugs and at least 1 day for daily drugs. The primary endpoint was gastric content that prevented examination, ended the procedure early, required intubation, or caused aspiration needing added monitoring, unplanned treatment, or admission.

The prespecified interim analysis included 60 patients, with 32 assigned to hold and 28 assigned to continue. Clinically significant residual gastric volume differed by 21.9%, with a 90% CI of 7.0 to 36.7 and P=.003. The trial stopped early after the result crossed the prespecified O’Brien-Fleming stopping boundary. Baseline characteristics, procedure indications, and preprocedure symptoms were similar between groups, and semaglutide, tirzepatide, dulaglutide, and oral semaglutide were represented. The interim analysis showed clear separation between the 2 medication strategies.

In the upper-endoscopy-only subgroup, clinically significant residual gastric volume occurred in 46.7% with continuation and 5.0% with holding, an absolute difference of 41.7%. The 90% CI was 17.9 to 65.4, and P=.001 in that subgroup. No patients in the combined upper endoscopy plus colonoscopy subgroup had the primary outcome, and those patients had clear liquids the day before the procedure. On univariate analysis, not undergoing colonoscopy was linked to higher risk of residual gastric volume, whereas HbA1c above 7% and GLP-1/GIP drug type were not associated. Among weekly medications, holding more than 3 days was linked to a higher proportion without the primary outcome, and events remained concentrated in upper endoscopy alone.

No unplanned intubation, aspiration, extended monitoring, or hospitalization was observed during the interim analysis. Patients with clinically significant residual gastric volume were predominantly asymptomatic on the procedure day, so symptom-based screening alone did not identify most cases in this sample. The study was not powered for uncommon safety outcomes and did not assess glycemic control after withholding one dose. It also excluded planned general anesthesia, chronic opioid use, and other gastric motility risk groups, narrowing generalizability.