Continuing GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonist therapy prior to elective upper endoscopy (EGD) increased the risk for significant residual gastric volume (RGV), but clear liquids the day before the procedure seemed to mitigate the risk, new research showed.

This randomized clinical trial compared holding with continuing the drug in this setting, and it was terminated early because of excessive risk for RGV to those who did not hold one drug dose prior to EGD.

“We hypothesized that continuing these medications would not significantly increase the risk of retained gastric contents since our practice prior to the new guidelines had not required us to hold these medications before endoscopy,” principal investigator Tilak Shah, MD, of Cleveland Clinic Florida in Weston, Florida, told Medscape Medical News.

“We had a sense during the study that perhaps there was a slight increase in risk based on subsequent retrospective studies published while we were conducting the trial,” he said. “But the close to 50% risk of retained solid food in patients who underwent upper endoscopy without a clear liquid diet the day before was far higher than we anticipated.” 

“On the other hand,” he added, “we found that no patients who consumed a clear liquid diet the day prior to the procedure — ie, those undergoing concurrent colonoscopy — had retained solid food, which is consistent with other retrospective studies.”

The study was published online in JAMA Internal Medicine.

‘Hold One Dose’

Researchers conducted a randomized, single-masked clinical trial at two large tertiary referral centers in the US of patients undergoing elective EGD while receiving GLP-1 or GLP-1/GIP agonists for at least 1 month between July 2024 and May 2025.

Participants were scheduled for EGD with or without colonoscopy, under moderate sedation or monitored anesthesia care. They were randomized to either continue their medication or hold one dose prior to the procedure.

All patients followed the usual fasting instructions prior to anesthesia. Those scheduled for EGD only were maintained on a regular diet the day before (stopping at midnight) and clear liquids up to 2 hours prior to the procedure.

Those who had a colonoscopy and upper endoscopy were placed on a clear liquid diet 24 hours before the procedure.

The main outcome was clinically significant RGV, a composite of gastric contents that precluded endoscopic examination; required premature termination or endotracheal intubation; and/or resulted in an aspiration event that led to extended observation or monitoring, unplanned therapeutics, or hospital admission.

There were 60 patients (32 holding one dose and 28 continuing medication) in the preplanned interim analysis. The median age was 62.5 years; and half were female.

Clinically significant RGV occurred in 3.1% in the hold group vs 25.0% in the continue group. This led to early termination of the trial, as risk exceeded the preestablished O’Brien-Fleming stopping boundary.

In the EGD-only subgroup (35 patients), clinically significant RGV occurred in 46.7% in the continue group vs 5.0% in the hold group.

In the EGD plus colonoscopy subgroup (25 patients), who were on clear liquids the day prior to the procedure, no clinically significant RGV events occurred in either group (hold or continue), and bowel preparation was deemed adequate in all patients.

On univariate regression analysis, not undergoing colonoscopy (ie, solid diet on the day prior to the procedure) was significantly associated with an increased risk for clinically significant RGV (odds ratio, 9.66). Neither GLP-1/GIP drug type nor A1c above 7% was associated with the primary outcome.

Additional analyses showed that among patients on weekly GLP-1/GIP medications, the proportion without clinically significant RGV was significantly higher for those who held the medication for more than 3 days (38 patients; 92.7%) than those who held for 3 days or less (five patients; 62.5%).

All cases of clinically significant RGV precluded endoscopic examination. However, there were no cases of unplanned endotracheal intubation, aspiration, or hospitalizations due to RGV.

Continuation of GLP-1 and/or GIP agonist therapy in the preprocedural setting was associated with a significant increase in RGV but did not increase the risk for other adverse events, the authors concluded.

“Notably,” they added, “patients who met the primary outcome were predominantly asymptomatic, indicating that symptom-based strategies may be insufficient for periprocedural risk stratification.”

Practice Changing

“In our own institution, the findings have already changed our practice,” Shah said. “We now recommend patients either consume a clear liquid diet or hold a dose of GLP-1 medication prior to upper endoscopy. We no longer recommend holding the medication before colonoscopy.”

Options for patients who have not held their medication or consumed clear liquids the day before but need an urgent procedure, he said, are point-of-care gastric ultrasound to assess if there is retained food, clear liquids and performing the procedure the following day, or performing the procedure under general anesthesia.

“Patients who consume a clear liquid diet on the day before the procedure, as is standard before a colonoscopy, do not need to hold the GLP-1 agonist just for the sake of decreasing risk of retained gastric contents,” he added.

Shah’s team currently is enrolling patients in OCULUS-2, a randomized trial comparing the effects of holding vs continuing GLP-1 and GIP agonists on bowel preparation quality.

‘Much-Needed Clarity’

“There has been a tremendous amount of controversy surrounding this topic, with serious head-butting between gastroenterologists and anesthesiologists,” said Rajiv Bhuta, MD, assistant professor of clinical gastroenterology and hepatology at Temple University and a gastroenterologist at Temple University Hospital, both in Philadelphia.

“This study is the first randomized controlled trial to provide real data on the issue and provides some much-needed clarity,” Bhuta, who was not involved in the study, told Medscape Medical News.

That said, he noted , “One caveat is that they did not specifically examine a group of EGD patients only on a clear liquid diet the day before in the nonhold group. We are extrapolating from the EGD/colonoscopy group that a clear liquid diet is likely sufficient, but we cannot exclude the possibility that the prep also (in addition to the clear liquids) is helping to cleanse the stomach.”

Overall, he concluded, “despite the initial upheaval, real-world data and research are now consistently demonstrating that a tailored, sensible approach to the pre-procedural management of these medications is both safe and nondisruptive for patients.”

The study was supported by the Cleveland Clinic Catalyst Grant and the American Society for Gastrointestinal Endoscopy Clinical Research Award. Shah and Bhuta reported having no conflicts.

Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.