Rethinking the Preoperative Hold in Patients on Incretin Therapy

Key Takeaways

• Guidance has moved from fixed withholding intervals toward risk-stratified continuation. Most patients on stable maintenance therapy can continue through an elective procedure.
• Time since the last dose is an imperfect predictor of retained gastric contents. Treatment phase, active gastrointestinal symptoms, and fasting adherence carry more information.
• Withholding is not risk-free, and labeling states that available data are insufficient to say whether interrupting therapy reduces retained gastric contents.

A patient on incretin therapy is scheduled for a colonoscopy, and the reflex is immediate: hold the drug. That reflex is three years old, it came from a real safety signal, and perioperative GLP-1 management has moved on without it. For clinicians whose panels increasingly include patients on glucagon-like peptide-1 (GLP-1) receptor agonists — including small-molecule oral agents — and dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonists, the preoperative question has become more specific than hold or continue.

Where the fixed interval came from

The 2023 American Society of Anesthesiologists consensus guidance took a precautionary and operationally simple position: withhold daily agents on the day of the procedure and weekly agents for one week beforehand, irrespective of indication, dose, or procedure type. Its simplicity is why it spread. A gastroenterology practice update later that year moved toward individualized decisions for endoscopy, suggesting that appropriately fasted patients without nausea, vomiting, dyspepsia, or abdominal distention could generally proceed as planned.¹ Multisociety guidance released in late 2024 went further, supporting continuation for most patients before elective procedures with additional precautions reserved for those at higher risk of delayed gastric emptying.² The reflex hardened faster than the evidence did.

Why the interval underperforms

The evidence separates into two findings that are often conflated. Retained gastric contents are genuinely more common: prospective gastric ultrasonography in 124 patients found them in 56% of those taking a once-weekly agent versus 19% of non-users despite guideline-concordant fasting, an adjusted prevalence ratio of 2.48 (95% CI, 1.23-4.97).³ Clinically evident aspiration is a different matter. A retrospective cohort of 366,476 adults undergoing 14 common surgical procedures found no significant difference in 30-day postoperative aspiration pneumonia (adjusted odds ratio, 0.78; 95% CI, 0.57-1.06).⁴ A separate analysis of patients with diabetes undergoing emergency surgery similarly found no increased risk of postoperative respiratory complications.⁵

Practically, this means retained contents are a risk marker, not an outcome—and that days since the last dose predicts them poorly. In the same ultrasonography study, duration of interruption showed no association with retained contents (adjusted odds ratio, 0.86; 95% CI, 0.65-1.14).³ Pharmacokinetics explain why: weekly agents have elimination half-lives of roughly five days to a week, so omitting one dose reduces recent exposure without reliably eliminating pharmacologic activity.¹

Three practical risk phenotypes

Lower risk describes a patient on a stable maintenance dose, without clinically significant gastrointestinal symptoms or known motility disorder, who has followed fasting instructions for an elective procedure. Continuation is reasonable.^1,2

Higher risk describes treatment initiation or dose escalation, higher-dose therapy, active symptoms — nausea, vomiting, bloating, early satiety, postprandial fullness, refractory constipation — uncertain fasting adherence, or comorbid conditions impairing motility. Mitigation options include a liquid-only diet for at least 24 hours, selective withholding, point-of-care gastric ultrasonography where available, or anesthesia-plan modification.^1,2

For urgent procedures, care should not be delayed for washout; patients are managed with full-stomach precautions.^1,2

What the evidence does not yet cover

Two limits belong in any conversation with an anesthesia colleague. The studies above enrolled patients on injectable agents, so they do not speak directly to the daily oral route now in use. And labeling for the approved small-molecule oral agent states plainly that available data are insufficient to inform mitigation recommendations, including whether modifying fasting or temporarily discontinuing the drug would reduce retained gastric contents.⁶

That is not a reason to default back to holding. It is a reason the preoperative note should name the agent and formulation, the dose and frequency, the treatment phase and any recent escalation, the most recent dose, current gastrointestinal symptoms, and any oral medications whose absorption delayed emptying could affect. "On a GLP-1" stratifies no one. Restarting deserves equal attention — resumption is guided by recovery of oral intake, postoperative nausea, ileus risk, and the administration requirements of the specific agent, and prolonged unintended discontinuation is a common, avoidable outcome.¹