Perioperative Management of SGLT2 Inhibitors in Patients with Heart Failure

Preoperative Recommendations

The American College of Cardiology recommends suspending empagliflozina at least 3 days before elective orthopedic surgery in hospitalized patients with heart failure to reduce the risk of perioperative metabolic acidosis 1, 2
The American Heart Association suggests suspending empagliflozina, canagliflozina, and dapagliflozina for at least 3 days before scheduled surgery, with a recommendation level of Class 1, LOE C-LD according to the ACC/AHA 2024 guidelines 1, 2, 3
Ertugliflozina should be suspended for at least 4 days before scheduled surgery 1, 2

SGLT2 inhibitors increase the risk of diabetic and euglycemic ketoacidosis in the perioperative period due to alterations in the insulin/glucagon ratio that favor ketone production even with normal glucose levels 4, 3, 5
The risk of perioperative ketoacidosis is significantly higher in patients taking SGLT2 inhibitors (1.02 vs 0.69 per 1000 patients; OR 1.48, 95% CI 1.02-2.15) 5

Patients with heart failure have a three-fold higher risk of perioperative mortality compared to patients with coronary artery disease without heart failure (9.2-9.3% vs 2.9% mortality at 30 days) 1

Preoperative (3 days before): suspend empagliflozina exactly 3 days before scheduled surgery, maintain adequate hydration to reduce the risk of ketosis, avoid prolonged fasting, and monitor capillary glucose and ketones 1, 2, 5, 6
Intraoperative: consider intravenous fluids with glucose if prolonged fasting is unavoidable, and monitor for signs of ketoacidosis (nausea, vomiting, abdominal pain, general weakness) 5, 6
Postoperative: reinstate empagliflozina once the patient is eating and drinking normally, usually 24-48 hours after surgery, and consider reinstating it as soon as possible to avoid decompensated heart failure 5

It is reasonable to continue guided medical therapy (GDMT) for compensated heart failure during the perioperative period, excluding SGLT2 inhibitors, unless contraindicated 1, 2
This includes ACE inhibitors/ARBs, beta-blockers, and mineralocorticoid antagonists, which should be reinstated as soon as clinically reasonable in the postoperative period 1, 2

The risk of ketoacidosis can occur even when patients have suspended SGLT2 inhibitors for >72 hours, emphasizing that the risk is a continuum 5
Ketoacidosis can present with normal or slightly elevated glucose levels (<200 mg/dL), known as "euglycemic ketoacidosis" 7, 6
Patients without diabetes can also develop euglycemic ketoacidosis with SGLT2 inhibitors 5
The risk of ketoacidosis is higher in emergency surgery than in elective surgery (1.1% vs 0.17%) 5, 6

In patients receiving SGLT2 inhibitors (e.g., empagliflozin), the drugs stimulate hepatic synthesis of β‑hydroxybutyrate and acetoacetate, raising circulating ketone concentrations and predisposing to euglycemic ketoacidosis during the peri‑operative period. 8

SGLT2 inhibitor therapy diminishes renal excretion of ketone bodies, prolonging ketonemia and further increasing the risk of peri‑operative ketoacidosis. 8

The American College of Cardiology recommends discontinuing empagliflozin at least 72 hours before elective surgery, and extending the hold to 96 hours in patients with moderate renal impairment (eGFR 30–60 mL/min/1.73 m²) or when the procedure carries a high bleeding risk. 9

The American College of Cardiology advises that empagliflozin should not be used in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m²) because drug exposure rises by roughly 52 % and urinary glucose excretion falls by about 68 %, leading to a contraindication per FDA labeling. 9