Jardiance and Anesthesia: Perioperative Interaction Guide

What does the Jardiance label say about surgery?

The Dosage and Administration section states: withhold JARDIANCE for at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting [1].

The ketoacidosis warning lists surgery among the precipitating conditions, alongside reduced caloric intake, volume depletion, acute febrile illness, ketogenic diet, under-insulinization from reduced or missed insulin doses, and alcohol abuse. It also names type 2 diabetes and pancreatic disorders (for example, a history of pancreatitis or pancreatic surgery) as risk factors [1]. The same section notes that urinary glucose excretion persists for about 3 days after the drug is stopped, and that postmarketing reports describe ketoacidosis or glucosuria lasting more than 6 days and sometimes up to 2 weeks after an SGLT2 inhibitor is discontinued [1].

Why fasting and surgery matter with empagliflozin

Empagliflozin blocks SGLT2 in the kidney so that more glucose leaves in the urine, lowering blood glucose independently of insulin, and it causes an osmotic diuresis [1]. The label lists reduced caloric intake, surgery, volume depletion and alcohol abuse as precipitating conditions for ketoacidosis, and it instructs that ketoacidosis be assessed regardless of the blood glucose level [1].

What perioperative euglycemic DKA looks like in reported cases

Three published case reports show the pattern.

A 59-year-old man with type 2 diabetes treated with insulin and empagliflozin took empagliflozin the day before a thoracoscopic debridement. After an overnight fast he was found to have euglycemic ketosis and acidosis during the operation; he was treated, woke from anesthesia normally, and the ketoacidosis resolved over the next 24 hours [2].

A 68-year-old woman became lethargic with worsening aphasia on the first day after resection of a temporal meningioma. She did not take empagliflozin on the day of surgery. Laboratory results showed bicarbonate 9 mmol/L, anion gap 21 and pH 7.2, with ketones in the urine and beta-hydroxybutyrate in the serum, and she was diagnosed with euglycemic diabetic ketoacidosis [3].

A 71-year-old man whose empagliflozin was never interrupted had a spinal fusion under general anesthesia. On postoperative day 2 his pH was 7.204, bicarbonate 10.1 mEq/L and glucose 178 mg/dL, and serum beta-hydroxybutyrate was 4.8 mmol/L. The acidosis persisted after a surgical explanation was treated, and it resolved within five days with empagliflozin discontinued and an insulin-dextrose infusion [4].

In an FDA Adverse Event Reporting System analysis by Blau and colleagues (reports through May 2015), three SGLT2 inhibitors accounted for 259 reports of acidosis, including 192 of ketoacidosis, versus 477 acidosis reports (71 ketoacidosis) for two DPP-4 inhibitors. The overall risk of acidosis was approximately 14-fold higher for the SGLT2 inhibitors, based on estimated exposure [5].

What are the warning signs?

The label lists nausea, vomiting, abdominal pain, generalized malaise and shortness of breath, consistent with dehydration and severe metabolic acidosis, and states that blood glucose at presentation may be below the level usually expected, for example less than 250 mg/dL [1]. It also says to consider ketone monitoring in patients with type 1 diabetes and in others at risk of ketoacidosis when the clinical situation indicates it [1]. Type 1 diabetes is not a recommended use for Jardiance, and the label says the drug significantly increases ketoacidosis risk in that group, with fatal cases reported [1].

What if surgery cannot wait 3 days?

The label's request is to withhold "if possible." Its ketoacidosis section says to consider ketone monitoring in patients at risk, to assess for ketoacidosis regardless of the presenting blood glucose, to discontinue Jardiance if ketoacidosis is suspected, and to monitor for resolution before restarting [1]. A 2024 review of perioperative medication management covering empagliflozin and dapagliflozin states that SGLT2 inhibitors have been associated with severe diabetic ketoacidosis and that discontinuation before surgery is imperative [6].

When can Jardiance be restarted after surgery?

The label gives two conditions: resume when the patient is clinically stable and has resumed oral intake [1], and monitor for resolution of ketoacidosis before restarting [1].

Anesthetic drugs, fluids and blood pressure

The label's table of clinically relevant interactions lists diuretics (more urine output and a higher chance of volume depletion), insulin and insulin secretagogues (hypoglycemia), lithium (serum lithium may fall), positive urine glucose tests, and an unreliable 1,5-AG assay [1]. Empagliflozin is metabolized by glucuronidation rather than by CYP enzymes, and the label states it does not inhibit or induce CYP450 enzymes [1].

The other perioperative concern the label flags is volume depletion, which can appear as symptomatic hypotension or an acute rise in creatinine, with higher risk at eGFR under 60, in older patients and in those taking loop diuretics [1]. In the pooled placebo-controlled trials, volume depletion events were reported in 0.3% on placebo, 0.5% on 10 mg and 0.3% on 25 mg [1]. In adult trials with basal insulin, hypoglycemia rates were 20.6% on placebo, 19.5% on 10 mg and 28.4% on 25 mg [1].

Does alcohol matter around surgery?

Alcohol abuse appears on the label's own list of conditions that can precipitate ketoacidosis [1].

What the anesthesia team needs to know

Three details from the label are relevant. The first is the dose: Jardiance is taken at 10 mg once daily, and for additional glycemic control in type 2 diabetes the dose may be increased to 25 mg once daily [1]. The second is the date of the last tablet, since the label's hold is at least 3 days where possible [1]. The third is whether insulin or a sulfonylurea is also being taken, a combination the label says increases hypoglycemia risk [1]. The label also lists the postoperative symptoms of ketoacidosis (nausea, vomiting, abdominal pain, malaise, shortness of breath) as signs that call for immediate medical attention [1].