Sodium–glucose cotransporter 2 (SGLT2) inhibitors have become a widely used class of medications for the management of type 2 diabetes mellitus, heart failure, and chronic kidney disease. Although agents such as empagliflozin, dapagliflozin, and canagliflozin offer significant cardiovascular and renal benefits, they also introduce specific perioperative risks that require careful planning and coordination among surgical, anesthesia, and medical teams. Awareness of the physiological impacts of SGLT2 inhibitors is essential to reduce preventable complications in the perioperative setting.
The most significant perioperative concern associated with SGLT2 inhibitors is the risk of euglycemic diabetic ketoacidosis. Unlike traditional diabetic ketoacidosis, this condition may occur with only mildly elevated or even normal blood glucose levels, making it more difficult to recognize. Surgical stress, perioperative fasting, reduced insulin dosing, dehydration, and acute illness all increase ketone production and reduce insulin activity, amplifying the risk when SGLT2 inhibitors are continued close to the time of surgery. Because hyperglycemia may be absent, diagnosis can be delayed unless clinicians maintain a high index of suspicion and monitor acid–base status and ketone levels appropriately.
Current perioperative recommendations generally advise discontinuing SGLT2 inhibitors several days before elective surgery. Most guidelines suggest holding these medications at least three days prior to surgery, and up to four days for agents with longer half-lives, to allow sufficient drug clearance and reduce ketone formation. This applies to both major and minor procedures requiring anesthesia or prolonged fasting. In urgent or emergent surgical cases where discontinuation is not possible, enhanced postoperative monitoring for metabolic acidosis and ketosis is critical.
Volume status is another important consideration. SGLT2 inhibitors promote osmotic diuresis and natriuresis, which can contribute to intravascular volume depletion. In the perioperative period, this effect may increase the risk of hypotension, acute kidney injury, and electrolyte disturbances, particularly when combined with preoperative fasting, bowel preparation, or intraoperative fluid shifts. Careful assessment of hydration status and judicious fluid management are therefore essential, especially in older patients or those with underlying renal dysfunction.
Renal function should be closely monitored before and after surgery in patients who have been taking SGLT2 inhibitors. Although these medications are renoprotective in the long term, perioperative hemodynamic changes may transiently reduce renal perfusion. Holding SGLT2 inhibitors preoperatively can help mitigate this risk, but postoperative resumption should be delayed until renal function has stabilized, oral intake has resumed, and the patient is hemodynamically stable.
Glycemic management during the period when SGLT2 inhibitors are withheld requires thoughtful planning. Alternative strategies, such as basal insulin or insulin infusions, may be necessary to maintain adequate glycemic control, particularly in patients with poorly controlled diabetes or those undergoing major surgery. Coordination with endocrinology can be beneficial in complex cases. Importantly, insulin therapy should not be overly reduced solely because glucose levels appear normal, as insufficient insulin may increase the risk of ketosis.
Postoperatively, SGLT2 inhibitors should only be restarted when the patient is eating reliably, free of acute illness or infection, and without evidence of metabolic acidosis. Early resumption in the setting of ongoing stress or limited caloric intake may precipitate euglycemic diabetic ketoacidosis. Clear documentation and communication regarding medication hold and restart plans are essential to avoid inadvertent errors during transitions of care.
As the use of SGLT2 inhibitors continues to expand across multiple clinical indications, perioperative protocols must evolve accordingly. Proactive identification of patients taking these agents, timely discontinuation before surgery, vigilant monitoring, and multidisciplinary communication are key components of safe perioperative management. For medical professionals, understanding these considerations is critical to minimizing risk while preserving the long-term benefits these medications provide.
