In a patient with type 2 diabetes mellitus taking a sodium‑glucose co‑transporter‑2 inhibitor (SGLT‑2 inhibitor) and a glucagon‑like peptide‑1 receptor agonist (GLP‑1 receptor agonist) scheduled for elective surgery, how should these medications be managed pre‑operatively?

Preoperative Management of SGLT-2 Inhibitors and GLP-1 Receptor Agonists

For patients with type 2 diabetes on SGLT-2 inhibitors and GLP-1 receptor agonists scheduled for elective surgery: continue GLP-1 receptor agonists through the perioperative period with aspiration risk mitigation strategies, and stop SGLT-2 inhibitors the day before surgery. 1

SGLT-2 Inhibitor Management

Timing of Discontinuation

• Stop SGLT-2 inhibitors the day before and the day of the procedure, which provides a minimum 36-hour gap if taken in the evening, or 48-52 hours if taken in the morning before a morning/afternoon procedure. 1, 2

• This pragmatic UK multidisciplinary consensus approach balances ketoacidosis risk against the harms of prolonged cessation (worsening heart failure, hyperglycemia, and surgical complications). 1

• The American Diabetes Association recommends a longer 3-4 day cessation period, though the 2025 UK consensus accepts the shorter approach as acceptable given pharmacokinetic profiles. 2

Critical Ketoacidosis Risk

• SGLT-2 inhibitors increase perioperative DKA risk 1.48-fold (1.02 vs 0.69 per 1000 patients, p=0.037), with the mechanism being increased renal glucose excretion triggering lipolysis and ketone production even with normal blood glucose. 1, 2

• Euglycemic ketoacidosis can occur in patients without diabetes taking SGLT-2 inhibitors for heart failure or chronic kidney disease, requiring vigilance in all patients on these medications. 1

• Ketoacidosis can occur even when SGLT-2 inhibitors are held for >72 hours, emphasizing that risk exists on a continuum without a defined safe threshold. 1, 2

• Emergency surgery patients have 6.5-fold higher ketoacidosis rates (1.1%) compared to elective surgery (0.17%). 1, 2

Perioperative Risk Mitigation

• Ensure patients remain well hydrated, avoid prolonged fasting periods, and monitor both glucose AND ketones perioperatively. 1

• In settings of unplanned or unavoidable prolonged fasting, consider glucose-containing intravenous fluids to mitigate ketone generation. 1

• Discuss the risk of perioperative ketoacidosis and mitigation strategies with the patient using shared decision-making. 1

Postoperative Resumption

• For outpatients discharged on the day of surgery, restart SGLT-2 inhibitors once eating and drinking normally (usually 24-48 hours after surgery). 1, 2

• For inpatients, restart SGLT-2 inhibitors only when eating and drinking normally AND capillary ketones are <0.6 mmol/L. 1, 2

Special High-Risk Scenario

• For patients on very low-energy/liver reduction diets before bariatric or laparoscopic surgery, stop SGLT-2 inhibitors at the commencement of the diet (typically 2-4 weeks preoperatively), as the combination creates severe ketoacidosis risk. 1, 2

GLP-1 Receptor Agonist Management

Continuation Strategy (Preferred Approach)

Continue GLP-1 receptor agonists through the perioperative period rather than discontinuing them, as the benefits of glycemic control outweigh aspiration risks when appropriate mitigation strategies are employed. 1, 3

• This recommendation prioritizes avoiding the harms of perioperative hyperglycemia and potential increase in postoperative major adverse cardiac events that occur with cessation. 1

• The 2025 UK multidisciplinary consensus from the Association of Anaesthetists, Royal College of Anaesthetists, and multiple specialty societies supports continuation with risk mitigation. 1

Risk Assessment and Stratification Required

Perform full risk assessment for aspiration risk including: 1

• Document indication and dose of GLP-1 receptor agonist, date commenced, dose variations, and last dose taken. 1

• Assess for symptoms of nausea, vomiting, or abdominal distention. 1

• Identify co-prescribed drugs that delay gastric emptying (opioids, proton pump inhibitors, tricyclic antidepressants). 1

• Document recent recreational drug use that delays gastric emptying (alcohol, cannabis). 1

• Note any previous gastro-esophageal surgery. 1

Aspiration Risk Mitigation Strategies (Mandatory)

Implement the following techniques to mitigate pulmonary aspiration risk: 1

• Perform point-of-care gastric ultrasound preoperatively to assess for residual gastric contents (target gastric volume <1.5 ml/kg). 1, 2

• Administer prokinetic drugs (metoclopramide or erythromycin) preoperatively to enhance gastric emptying. 1, 2

• Use rapid-sequence intubation with full airway protection rather than supraglottic airways, as case reports document aspiration with supraglottic devices. 1, 2

• Adhere to recommended fasting guidelines and avoid prolonged starvation times. 1

• Consider postponing elective procedures if patient has recently started medication, increased dose, or is experiencing gastrointestinal symptoms. 1

Alternative Cessation Approach (If Continuation Not Feasible)

If shared decision-making determines that continuation poses unacceptable risk, use the following cessation protocol: 1, 2

• Hold weekly GLP-1 receptor agonists (semaglutide, dulaglutide) for 3 weeks (three half-lives) before elective surgery to allow clearance of approximately 88% of the drug. 1, 2

• Hold daily GLP-1 receptor agonists (liraglutide) for 3-4 days before surgery. 2

• Discontinuation for only 1 week is inadequate, as studies demonstrate this shorter period does not decrease the prevalence of retained gastric contents (24.2% of patients on semaglutide have residual gastric content vs 5.1% of controls, even after 12+ hour fasting). 1, 2

Diabetes-Specific Considerations

• For patients with diabetes mellitus taking GLP-1 receptor agonists, consult endocrinology to weigh glycemic control benefits against aspiration risk, as prolonged cessation may have detrimental effects on perioperative glycemic control. 1, 2

• Consider bridging diabetic therapy if GLP-1 receptor agonists are held for longer than the next scheduled dosing time. 1

Common Pitfalls to Avoid

• Never assume normal glucose levels exclude ketoacidosis in patients on SGLT-2 inhibitors – euglycemic DKA can occur with glucose <11.0 mmol/L, requiring ketone and pH monitoring. 1, 2

• Never restart SGLT-2 inhibitors postoperatively without confirming ketones <0.6 mmol/L, even if the patient is eating and drinking normally. 1, 2

• Never use supraglottic airways in patients on GLP-1 receptor agonists – case reports document aspiration events requiring full airway protection with rapid-sequence intubation. 1, 2

• Never assume 1 week cessation of weekly GLP-1 receptor agonists is adequate – this does not decrease retained gastric contents and requires 3 weeks for adequate clearance. 1, 2

• Never discontinue SGLT-2 inhibitors in patients on very low-energy diets without stopping them at diet commencement – the combination creates severe ketoacidosis risk requiring 2-4 week preoperative cessation. 1, 2