In patients admitted to the intensive care unit, should sodium‑glucose cotransporter‑2 (SGLT‑2) inhibitors be discontinued, and what criteria allow safe restarting?

SGLT2 Inhibitors in Critical Care: Discontinuation and Restarting Criteria

In critically ill ICU patients, SGLT2 inhibitors should be temporarily discontinued immediately upon admission due to high risk of euglycemic ketoacidosis, volume depletion, and acute kidney injury in the setting of acute illness, prolonged fasting, and metabolic stress. 1, 2, 3

Immediate Discontinuation Criteria in the ICU

SGLT2 inhibitors must be withheld in the presence of any of the following precipitating factors commonly encountered in critical care:

• Acute severe illness or sepsis – the metabolic stress increases insulin resistance and risk of ketoacidosis 1, 2, 3
• Prolonged fasting or NPO status – including pre-operative preparation or inability to maintain oral intake 1, 2
• Severe volume depletion or hemodynamic instability – SGLT2 inhibitors cause osmotic diuresis that exacerbates hypovolemia 1, 2
• Major surgery or procedures – withhold at least 3 days before major surgery if possible 2, 4
• Reduced insulin dosing or insulin deficiency states – relative or absolute insulin deficiency precipitates ketoacidosis 1, 2
• Ketogenic diet or severe caloric restriction – common in ICU patients with poor oral intake 2

The FDA label explicitly states to withhold dapagliflozin for at least 3 days prior to major surgery or procedures with prolonged fasting, and to resume only when clinically stable with resumed oral intake. 2

Monitoring for Ketoacidosis During ICU Stay

Critical care providers must maintain high suspicion for euglycemic DKA, as blood glucose may be normal or only mildly elevated (< 250 mg/dL, sometimes as low as 127 mg/dL). 1

When any ICU patient on SGLT2 inhibitors presents with concerning symptoms, immediately assess:

• Serum beta-hydroxybutyrate – the gold standard; > 3.0 mmol/L indicates significant ketosis requiring treatment 1
• Venous blood gas pH – pH < 7.3 meets DKA diagnostic threshold 1
• Anion gap and bicarbonate – assess metabolic acidosis severity 1
• Clinical symptoms – nausea, vomiting, abdominal pain, weakness, dyspnea, even with normal glucose 1, 2

Do not rely solely on urine ketones; serum beta-hydroxybutyrate provides more specific quantitative assessment. 1 Urinary glucose excretion persists for 3 days after discontinuation, and ketoacidosis has been reported lasting up to 2 weeks post-discontinuation in some cases. 2

Treatment Protocol for SGLT2-Associated Ketoacidosis

If beta-hydroxybutyrate > 3.0 mmol/L and pH < 7.3:

• Diagnose DKA and discontinue SGLT2 inhibitor immediately 1
• Initiate standard DKA management with insulin infusion plus IV fluids 1
• Add glucose-containing IV fluids even when blood glucose is normal to prevent hypoglycemia and suppress ketogenesis 1
• Monitor for resolution before considering restart 2

If beta-hydroxybutyrate 1.5–3.0 mmol/L with normal pH:

• Temporarily withhold SGLT2 inhibitor 1
• Ensure adequate hydration with glucose-containing fluids 1
• Address precipitating factors (resume normal diet, avoid fasting) 1
• Monitor ketones and clinical status closely 1

Criteria for Safe Restarting After ICU Discharge

Restart SGLT2 inhibitors only when ALL of the following conditions are met:

• Capillary or serum beta-hydroxybutyrate < 0.6 mmol/L (ideally; must be < 1.5 mmol/L at minimum) 1
• Patient eating and drinking normally with established oral intake 1
• Precipitating acute illness has fully resolved – no ongoing sepsis, hemodynamic stability achieved 1
• Clinical stability confirmed – typically 24–48 hours after normal oral intake is re-established 1
• No ongoing fasting or surgical procedures planned in the immediate future 1

For post-operative patients, the 24–48 hour window after resuming oral intake applies when no metabolic complications occurred peri-operatively. 1

Special Considerations for Heart Failure Patients in ICU

While the above discontinuation guidance applies to acute critical illness, there is nuanced evidence regarding in-hospital initiation for stabilized heart failure patients:

• For patients hospitalized with worsening HFrEF who have stabilized, in-hospital initiation of SGLT2 inhibitors is supported by strong evidence showing reduced 30-day mortality and readmission rates 5
• The SOLOIST-WHF trial demonstrated safety and efficacy of SGLT2 inhibitor initiation either pre-discharge or early post-discharge in hospitalized heart failure patients 5
• SGLT2 inhibitors have minimal blood pressure effects, no excess kidney injury risk, and rapid clinical benefits accruing within days to weeks 5

However, this applies only to hemodynamically stable, euvolemic patients who are eating normally—NOT to acutely decompensated or critically ill ICU patients. 5 The distinction is critical: location of care (ICU vs. ward) matters less than objective clinical stability (vital signs, volume status, oral intake, absence of acute metabolic derangement). 5

Renal Function Considerations

• SGLT2 inhibitors may be continued even if eGFR falls below 20 mL/min/1.73 m² during treatment, provided the patient is not on kidney replacement therapy 1
• After successful restart following DKA recovery, continuation is justified by cardiovascular and renal protective benefits despite modest kidney function decline 1
• However, during acute kidney injury in the ICU setting, temporary discontinuation is prudent until renal function stabilizes 2

Common Pitfalls to Avoid

• Do not dismiss symptoms because glucose is normal – euglycemic DKA is the hallmark of SGLT2-associated ketoacidosis 1, 2
• Do not continue SGLT2 inhibitors during acute critical illness despite their long-term benefits in heart failure – the acute metabolic risks outweigh benefits during unstable periods 1, 2, 3
• Do not restart prematurely before confirming ketone normalization and oral intake – this risks recurrent ketoacidosis 1
• Do not forget patient education – all patients restarted on SGLT2 inhibitors must understand sick-day rules and when to discontinue during future acute illness 1, 2