Patients on GLP-1 or GLP-1/GIP agonists had significant residual gastric volume if the medication was not held prior to upper endoscopy, unless they were on a clear liquid diet the previous day, according to a study published March 16 in JAMA Internal Medicine.
As GLP-1 and GIP agonists such as semaglutide and tirzepatide have become widely prescribed, physicians have been grappling with whether patients should stop taking them before undergoing sedated procedures. The concern centers on a known side effect of these medications, delayed gastric emptying, which can leave food and fluid sitting in the stomach longer than expected, potentially raising the risk of aspiration during anesthesia.
The clinical trial, conducted at two Cleveland Clinic centers, enrolled 60 adults undergoing elective upper endoscopy, all of whom had been on a stable dose of a GLP-1 or GIP agonist for at least one month. The trial was stopped early after an interim analysis found results so striking they crossed a preset statistical stopping boundary. The primary outcome — clinically significant residual gastric volume — was defined as retained gastric contents that either prevented the endoscopy from being completed, required premature termination or emergency intubation, or led to an aspiration event requiring extended monitoring or hospitalization.
Here are 10 things to know:
1. Patients who continued their GLP-1/GIP medication had a 25% rate of clinically significant RGV, compared to just 3.1% in those who held one dose, nearly an eightfold difference.
2. The results were so striking that the study hit its preestablished stopping boundary at the 50% enrollment mark and was terminated early.
3. In the subgroup that underwent only an upper endoscopy — and ate a regular diet the day before — the RGV rate was 46.7% in the “continue” group compared to just 5% in the “hold” group.
4. Patients who also had a colonoscopy, and therefore followed a clear liquid diet the day before, had zero cases of clinically significant RGV in either group, suggesting diet prep may eliminate the risk regardless of whether medication is held.
5. While retained stomach contents were far more common in the continue group, there were no cases of aspiration, unplanned intubation or hospitalizations. However, the study was not designed to detect these rarer events, and the authors cautioned that the absence of observed events should not be interpreted as a safety signal.
6. None of the patients who developed clinically significant RGV reported any upper GI symptoms, such as nausea or vomiting, beforehand, meaning clinicians cannot rely on asking how patients feel as a screening strategy.
7. Among patients on weekly GLP-1/GIP drugs, those who held their medication for more than three days were significantly more likely to have a clear stomach than those who held it for three days or fewer (92.7% vs. 62.5%).
8. Prior guidance from the American Society of Anesthesiologists was based only on retrospective, observational data. The trial is the first prospective randomized study to directly test holding versus continuing these medications before a sedated procedure.
9. Neither the specific GLP-1/GIP medication used nor HbA1c above 7% were associated with increased RGV risk, suggesting the effect may be a class-wide phenomenon rather than tied to any particular drug or degree of diabetes severity.
10. Because patients with retained gastric contents were largely asymptomatic, the authors argue that symptom-based screening is an insufficient tool for periprocedural risk stratification, and that clinicians should not use the absence of GI complaints as reassurance that a patient’s stomach is clear.
