What is the management plan for an insulin-dependent type 2 diabetic patient on Canagliflozin (SGLT2 inhibitor) presenting with nausea, vomiting, and severe hyperglycemia after missing insulin doses for 2 days?

Management of Suspected Euglycemic Diabetic Ketoacidosis in an Insulin-Dependent Type 2 Diabetic on Canagliflozin

This patient requires immediate assessment for euglycemic diabetic ketoacidosis (DKA), discontinuation of canagliflozin, aggressive fluid resuscitation, continuous IV insulin infusion with early dextrose supplementation, and close monitoring—even though the glucose of 25.7 mmol/L (463 mg/dL) appears elevated, the combination of SGLT2 inhibitor use, missed insulin doses, and gastrointestinal symptoms creates high risk for ketoacidosis that may worsen rapidly. 1, 2

Immediate Diagnostic Workup

Obtain stat laboratory studies including:

• Venous blood gas (pH and bicarbonate) 3, 1
• Serum β-hydroxybutyrate (preferred over urine ketones, as nitroprusside methods miss the predominant ketone body) 3, 1
• Complete metabolic panel with electrolytes, BUN, creatinine, calcium, phosphorus 3, 1
• Blood glucose confirmation 3
• Serum osmolality 3

High clinical suspicion is mandatory because SGLT2 inhibitors like canagliflozin cause euglycemic DKA where glucose may be normal or only mildly elevated (<250 mg/dL), masking severe underlying ketoacidosis. 3, 1, 2 The nausea and vomiting in this context are red flags for ketoacidosis regardless of glucose level. 3, 1, 2

Immediate Interventions

Discontinue Canagliflozin

Stop the SGLT2 inhibitor immediately upon suspicion of ketoacidosis. 1, 4, 2 The FDA drug label explicitly warns that canagliflozin significantly increases ketoacidosis risk, with fatal events reported in type 2 diabetics. 2 Precipitating factors include under-insulinization from missed insulin doses (as in this case), acute illness, reduced caloric intake, vomiting, and volume depletion. 2

Fluid Resuscitation

Administer isotonic saline (0.9% NaCl) at 15-20 mL/kg/hr in the first hour to restore circulatory volume. 1 SGLT2 inhibitors cause intravascular volume depletion, and this patient's vomiting compounds the risk. 2 Continue aggressive hydration at 1.5 times maintenance requirements (approximately 5 mL/kg/hr) after initial resuscitation. 3

Insulin Therapy with Critical Modification

Start continuous IV regular insulin at 0.1 units/kg/hr after initial fluid resuscitation. 3, 1

Critical difference from typical DKA management: Add dextrose-containing fluids immediately once insulin is started, even though glucose is elevated. 1 In euglycemic DKA associated with SGLT2 inhibitors, dextrose is needed early to:

• Prevent hypoglycemia as insulin drives glucose down 1
• Induce endogenous insulin secretion to help stop ketogenesis 1
• Maintain adequate glucose substrate while clearing ketones 1

For mild DKA (if confirmed), a priming dose of 0.4-0.6 units/kg can be given (half IV bolus, half subcutaneous/intramuscular), followed by 0.1 unit/kg subcutaneously or intramuscularly every hour. 3

Potassium Replacement

Begin potassium replacement when serum levels fall below 5.2 mEq/L (provided adequate urine output exists), as insulin therapy drives potassium intracellularly. 3, 1 Typical replacement is 20-30 mEq per liter of IV fluid, using 1/3 potassium phosphate and 2/3 potassium chloride or acetate. 3, 1

Monitoring Requirements

Check blood glucose every 1-2 hours until stable. 1 If glucose doesn't fall by 50-75 mg/dL in the first hour, double the insulin infusion rate. 1

Monitor electrolytes, BUN, creatinine, and venous pH every 2-4 hours. 3, 1 Arterial blood gases are generally unnecessary; venous pH (approximately 0.03 units lower than arterial) and anion gap adequately monitor acidosis resolution. 3

Check serum potassium every 2-4 hours due to life-threatening hypokalemia risk with insulin therapy. 1

Measure serum β-hydroxybutyrate directly rather than relying on urine ketones for accurate monitoring of ketoacidosis resolution. 3, 1

Resolution Criteria and Transition

DKA is resolved when:

• Glucose <200 mg/dL 3
• Serum bicarbonate ≥18 mEq/L 3
• Venous pH ≥7.3 3
• Normalized ketones 1

Continue IV insulin until ketoacidosis resolves, not just until glucose normalizes. 1 This is a critical pitfall—stopping insulin when glucose normalizes but before ketones clear will cause recurrent ketoacidosis.

Administer subcutaneous basal insulin 2-4 hours before discontinuing IV insulin to prevent recurrence. 1 Continue IV insulin for 1-2 hours after starting subcutaneous regimen to ensure adequate plasma insulin levels. 3 Abrupt discontinuation of IV insulin without overlapping subcutaneous coverage leads to poor glycemic control and ketoacidosis recurrence. 3, 1

Special Considerations for SGLT2 Inhibitor-Associated DKA

Urinary glucose excretion persists for 3 days after discontinuing canagliflozin, with postmarketing reports of ketoacidosis and glucosuria lasting >6 days and up to 2 weeks after SGLT2 inhibitor discontinuation. 2 Monitor for prolonged ketoacidosis duration beyond typical DKA. 2

Do not restart canagliflozin. 1, 4, 2 The American College of Cardiology and FDA recommend avoiding SGLT2 inhibitors in patients with history of ketoacidosis, and this patient has demonstrated susceptibility. 4, 2

Common Pitfalls to Avoid

The most dangerous error is dismissing ketoacidosis because glucose appears reassuring or only moderately elevated. 1 SGLT2 inhibitors cause glycosuria that prevents glucose accumulation while ketoacidosis progresses unchecked. 1

Inadequate potassium replacement can lead to life-threatening cardiac arrhythmias and respiratory muscle weakness. 3, 1

Stopping IV insulin when glucose normalizes but before ketones clear will cause recurrent ketoacidosis. 1

Failing to overlap subcutaneous and IV insulin during transition leads to insulin gap and metabolic decompensation. 3, 1

Discharge Planning and Prevention

Educate the patient to never discontinue insulin during illness. 1, 4, 2 This patient's missed insulin doses for 2 days was a critical precipitating factor. 2

Do not restart canagliflozin. Consider alternative glucose-lowering agents such as DPP-4 inhibitors or GLP-1 receptor agonists that don't carry ketoacidosis risk. 3

Provide sick-day management education: maintain hydration, continue insulin (possibly at reduced doses), monitor ketones when unwell, and seek immediate care for nausea, vomiting, abdominal pain, or dyspnea. 1, 4, 2

Establish a multiple-dose insulin regimen using combination of short/rapid-acting and intermediate/long-acting insulin before discharge. 3 Ensure the patient understands proper insulin administration and has adequate supplies. 3