Study confirms GLP-1 and GIP agonists should be paused prior to elective upper endoscopy

medwireNews: Continuing glucagon-like peptide (GLP)-1 agonist therapy alone or with glucose-dependent insulinotropic polypeptide (GIP) agonist therapy prior to elective upper endoscopy significantly increases the risk for a clinically significant residual gastric volume (RGV) compared with pausing treatment ahead of the procedure, warn US investigators.

The team defined clinically significant RGV as a composite endpoint of patients having gastric contents that prevented endoscopy, required premature termination or endotracheal intubation, and/or aspiration leading to extended observation or monitoring, unplanned therapeutics, or hospital admission.

“Notably, patients who met the primary outcome were predominantly asymptomatic, indicating that symptom-based strategies may be insufficient for periprocedural risk stratification,” write Tilak Shah (Cleveland Clinic Florida, Weston) and colleagues in JAMA Internal Medicine, who suggest that a clear liquid diet on the day prior to the procedure may “eliminate” the risk.

A widely adopted recommendation

Concerns that the delayed gastric emptying associated with GLP-1/GIP agonists use could increase the risk for regurgitation and pulmonary aspiration of gastric contents during sedation or general anesthesia led to a recommendation from the American Society of Anesthesiologists that patients taking a daily GLP-1 agonist hold their dose on the day of a procedure, while those on a weekly dose hold for a week before the procedure. This advice was rapidly incorporated into routine practice for sedated procedures such as endoscopy, the authors say.

To investigate further, the team recruited adults scheduled for an elective upper endoscopy procedure, with or without colonoscopy, under monitored anesthesia care or moderate sedation who were taking a stable dose of a GLP-1 or GLP-1/GIP agonist for at least 1 month.

Between July 2024 and May 2025, 396 patients at two tertiary care centers were invited to take part. Of these, 68 were randomly assigned to continue their medication at the same dosage and scheduled times, or to hold one dose of their medication prior to upper endoscopy, giving a medication-free period of at least 1 day for daily medications, or 7–13 days for weekly medications.

After exclusions, 32 randomly assigned to the hold group and 28 to the continue group were included in a preplanned interim analysis when 50% of the target sample size was reached.

The median age was 63 years in the hold and continue treatment groups; 53% and 45% were men, respectively, 31% and 25% had diabetes, and the median duration of GLP-1/GIP agonist use was 6 months in both treatment groups.

Twenty patients in the hold treatment group and 15 in the continue treatment group underwent upper endoscopy alone and had only clear liquids 2 hours beforehand, while the remaining patients also had a colonoscopy and followed a clear liquid diet for 24 hours before the procedure.

A marked increase in clinically significant RGV

Intention-to-treat analysis revealed that there was a clinically significant difference in the primary outcome of clinically significant RGV, with rates of 3.1% in the hold group and 25.0% among those asked to continue their medication, at an absolute significant difference of 21.9%.

“All cases of clinically significant RGV occurred in the upper endoscopy-only subgroup,” the researchers say, with rates of 5.0% versus 46.7% in the hold and continue groups, respectively, giving an absolute significant difference of 41.7%.

The study was terminated early as the primary outcome p value of 0.0029 was less than the prespecified value of 0.0054 stopping boundary for safety and futility.

Liquid diet may reduce RGV risk

The authors report that there were no “unanticipated cases of endotracheal intubation, aspiration, extended monitoring, or hospitalization” in the study.

Univariate regression analysis indicated that having endoscopy alone (ie, a solid diet on the day before the procedure) was associated with a significantly increased risk for clinically significant RGV, at an odds ratio of 9.66 versus having endoscopy and colonoscopy after a liquid diet. Neither GLP-1/GIP agonist drug type nor elevated glycated hemoglobin were associated with clinically significant RGV.

Among patients receiving weekly GLP-1/GIP agonists, there was no clinically significant RGV in 92.7% of patients who held their medication for more than 3 days versus 62.5% of those who held them for 3 days or less.

The researchers note that no patient with clinically significant RGV reported upper gastrointestinal symptoms on the day of the procedure, such as heartburn or dyspepsia, whereas one patient without increased RGV experienced nausea and vomiting.

“While not a specific aim of this study, screening patients on these medications for symptoms is often a decision point in periprocedural management,” they write, “and therefore, this finding should be taken into consideration when creating future care paths.”

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JAMA Intern Med 2026; doi:10.1001/jamainternmed.2026.0027