What medications should be avoided in a patient with diabetic ketoacidosis (DKA)?

Medications to Avoid in Diabetic Ketoacidosis

SGLT2 inhibitors must be immediately discontinued in any patient with DKA and should not be restarted until the patient is metabolically stable, as these agents can precipitate or worsen euglycemic ketoacidosis. 1, 2

Critical Medications to Discontinue Immediately

SGLT2 Inhibitors (Highest Priority)

• Discontinue dapagliflozin, empagliflozin, canagliflozin, and all other SGLT2 inhibitors immediately upon DKA diagnosis, as they promote ketogenesis through altered insulin/glucagon ratios and can cause life-threatening euglycemic DKA even with normal glucose levels 1, 3, 2
• These medications should be stopped 3-4 days before any planned surgery or during acute illness to prevent DKA 1, 3
• Do not restart SGLT2 inhibitors until infection is resolved and the patient is metabolically stable, typically not until 3-4 days after acute illness resolution 1

Metformin (Critical in Specific Contexts)

• Metformin must be avoided or discontinued in DKA patients due to the risk of lactic acidosis, particularly when dehydration, renal impairment, or tissue hypoperfusion is present 4
• Stop metformin immediately if serum creatinine is ≥1.5 mg/dL in men or ≥1.4 mg/dL in women 4
• Discontinue during dehydration states, as metformin accumulation can lead to fatal lactic acidosis 4

Medications Requiring Dose Adjustment or Caution

Sulfonylureas

• Reduce or discontinue sulfonylureas when initiating DKA treatment to prevent hypoglycemia during insulin therapy 4, 1
• First-generation sulfonylureas (chlorpropamide, tolazamide, tolbutamide) should be avoided entirely in patients with any degree of renal impairment, which is common in DKA 4
• If HbA1c is well-controlled at baseline, wean or stop sulfonylureas before starting intensive insulin therapy 4

Insulin Adjustments

• Reduce total daily insulin dose by approximately 20% when transitioning from DKA management if the patient was previously on insulin, to prevent hypoglycemia 4, 1
• Never stop intravenous insulin abruptly; administer basal subcutaneous insulin 2-4 hours before discontinuing IV insulin to prevent rebound ketoacidosis 1, 2

Medications That Should NOT Be Given During Active DKA

Bicarbonate (Controversial but Generally Avoided)

• Bicarbonate administration is NOT recommended for DKA patients with pH >6.9-7.0, as multiple studies show no benefit in resolution time and it may worsen ketosis, cause hypokalemia, and increase cerebral edema risk 4, 1, 2
• The American Diabetes Association explicitly recommends against bicarbonate use in this pH range 1

Potassium-Sparing Agents (Conditional)

• Delay insulin therapy if serum potassium is <3.3 mEq/L and avoid potassium-sparing diuretics or supplements until adequate renal function is confirmed, as insulin will further lower potassium levels 1
• Mineralocorticoid receptor antagonists should be used with extreme caution given the risk of hyperkalemia in the setting of renal impairment 4

Special Considerations and Clinical Pitfalls

DPP-4 Inhibitors

• Discontinue DPP-4 inhibitors before starting GLP-1 receptor agonists if transitioning diabetes management post-DKA 4

Diuretics

• Reduce or hold loop and thiazide diuretics during active DKA treatment, as they exacerbate dehydration, electrolyte disturbances, and pre-renal azotemia 4
• Aggressive fluid resuscitation may require temporary discontinuation of diuretics to restore intravascular volume 4, 1

Medications to Avoid Due to Renal Impairment

• Nateglinide should be used with extreme caution as active metabolites accumulate with decreased kidney function, which is common in DKA 4
• Glyburide should be avoided in favor of glipizide if a sulfonylurea is absolutely necessary, as glyburide has active metabolites that accumulate 4

Key Clinical Pearls

• The most critical medication error in DKA is premature discontinuation of insulin therapy before complete resolution of ketosis, which can lead to recurrent DKA 1
• Always identify and treat precipitating factors such as infection, myocardial infarction, or stroke, which may require discontinuation of other medications 4, 1
• Monitor for drug interactions: gemfibrozil increases levels of repaglinide and rosiglitazone, requiring dose reductions if these agents are used 4
• Patients on chronic SGLT2 inhibitor therapy are at ongoing risk for euglycemic DKA during any acute illness, infection, trauma, surgery, or fasting state 3, 2, 5