How does treatment for euglycemic ketoacidosis associated with SGLT2 (sodium-glucose cotransporter 2) inhibitors differ from treatment for alcoholic ketoacidosis?

Treatment Differences: SGLT2i-Associated Euglycemic Ketoacidosis vs. Alcoholic Ketoacidosis

While both SGLT2i-associated euglycemic ketoacidosis and alcoholic ketoacidosis share similar treatment principles (IV fluids, dextrose, and insulin), the critical difference is that SGLT2i-associated ketoacidosis requires immediate and permanent discontinuation of the offending medication, whereas alcoholic ketoacidosis requires thiamine supplementation and abstinence from alcohol.

Core Treatment Similarities

Both conditions require the same fundamental metabolic resuscitation approach:

• Aggressive IV fluid resuscitation to correct volume depletion and improve tissue perfusion 1, 2
• Dextrose infusion (5% dextrose) to suppress ketogenesis while maintaining euglycemia 1, 3
• Insulin therapy (intravenous) to halt ketone production, even in the presence of normal glucose levels 1, 3, 4
• Electrolyte monitoring and replacement, particularly potassium supplementation as acidosis corrects 1
• Serial monitoring of anion gap, beta-hydroxybutyrate levels, and pH until complete resolution 1, 2

Critical Differences in Management

SGLT2i-Associated Euglycemic Ketoacidosis

Medication discontinuation is mandatory:

• Immediately discontinue the SGLT2 inhibitor upon diagnosis 5, 1
• Hold the medication during acute illness, surgery, or critical medical illness 5
• Discontinue 3 days before elective procedures (4 days for ertugliflozin) 5
• Consider permanent discontinuation if severe or recurrent episodes occur 6

Insulin management specifics:

• Continue IV insulin with dextrose infusion for approximately 72-90 hours until acidosis resolves 1, 3
• Avoid substantial initial insulin dose reductions (>20%) when restarting SGLT2i therapy 5
• Maintain at least low-dose insulin in insulin-requiring individuals to prevent recurrence 6

Prevention education:

• Implement "STOP DKA" protocol: Stop SGLT2 inhibitor, Test for ketones, maintain fluid and carbohydrate intake 5
• Educate patients to discontinue during intercurrent illness (nausea, vomiting, diarrhea) 5, 1
• Counsel on early recognition of nonspecific symptoms (malaise, nausea, vomiting, abdominal pain) despite normal glucose 5

Alcoholic Ketoacidosis

Thiamine administration is essential:

• Administer thiamine (100mg IV) before or concurrent with dextrose to prevent Wernicke encephalopathy
• This is unique to alcoholic ketoacidosis and not required for SGLT2i-associated cases

Alcohol cessation:

• Address underlying alcohol use disorder
• No medication discontinuation required (unlike SGLT2i cases)
• Focus on nutritional rehabilitation and vitamin supplementation

Faster resolution:

• Typically resolves more rapidly (24-48 hours) compared to SGLT2i-associated cases which may take 72-90 hours 1, 3

Diagnostic Considerations

SGLT2i-associated euglycemic ketoacidosis is particularly challenging to diagnose:

• Blood glucose often normal or only mildly elevated (<200 mg/dL) 5, 1, 2
• High anion gap metabolic acidosis with ketonemia (beta-hydroxybutyrate >3 mmol/L) 1, 3
• Absence of significant hyperglycemia delays recognition by both patients and providers 2
• Consider in any patient on SGLT2i presenting with metabolic acidosis, especially perioperatively 3, 7, 4

Common precipitating factors for SGLT2i-associated cases:

• Decreased oral intake, fasting, or perioperative state 7, 2
• Intercurrent illness with vomiting and dehydration 1
• Insulin dose reduction or omission 1, 2
• Surgery or prolonged fasting 5, 3, 4

Risk Mitigation Strategies

For patients on SGLT2 inhibitors:

• Withhold during prolonged fasting, surgery, or critical illness 5
• Implement sick day rules with clear instructions to stop medication 5
• Avoid in patients with type 1 diabetes except with extensive counseling and close monitoring 2
• Monitor closely in non-diabetic patients receiving SGLT2i for heart failure 7

Common Pitfalls

• Do not confuse euglycemic ketoacidosis with simple hyperglycemia—the absence of significant hyperglycemia is the hallmark of SGLT2i-associated cases 2
• Do not delay insulin therapy waiting for glucose to rise—start insulin with dextrose immediately 1, 3
• Do not restart SGLT2i too early—ensure complete resolution of acidosis before considering reinitiation 4
• Do not forget thiamine in alcoholic ketoacidosis—this is a critical difference from SGLT2i cases

5, 6, 1, 3, 7, 2, 4