Is Jardiance (empagliflozin) contraindicated in diabetic ketoacidosis (DKA)?

Is Jardiance Contraindicated in DKA?

Yes, Jardiance (empagliflozin) is absolutely contraindicated during active diabetic ketoacidosis and must be discontinued immediately if DKA is suspected. 1

FDA-Mandated Contraindication and Black Box Warning

• Jardiance is not indicated for treatment of diabetic ketoacidosis and carries an FDA warning that ketoacidosis—including fatal cases—has been reported in patients taking SGLT2 inhibitors like empagliflozin. 1
• The FDA label explicitly states that Jardiance is "not recommended for patients with type 1 diabetes or for the treatment of diabetic ketoacidosis." 1
• Reports of ketoacidosis requiring urgent hospitalization have been identified in postmarketing surveillance for both type 1 and type 2 diabetes patients receiving SGLT2 inhibitors, with fatal outcomes documented. 1

Clinical Mechanism: Why SGLT2 Inhibitors Cause and Worsen DKA

• SGLT2 inhibitors like Jardiance increase the risk of euglycemic diabetic ketoacidosis—a particularly dangerous presentation where blood glucose may be normal or only mildly elevated (often <250 mg/dL), making diagnosis challenging and frequently delayed. 2, 3, 4
• The mechanism involves continued renal glucose excretion that suppresses insulin secretion while simultaneously increasing glucagon, promoting ketogenesis even without marked hyperglycemia. 3, 5
• Euglycemic DKA presents with malaise, nausea, vomiting, abdominal pain, and dyspnea but without the expected severe hyperglycemia, leading emergency physicians to miss the diagnosis unless they specifically check ketones and arterial blood gases. 3, 6

Predisposing Risk Factors That Trigger DKA on SGLT2 Inhibitors

• Acute illness with reduced oral intake, fever, vomiting, or diarrhea significantly elevates DKA risk and mandates immediate discontinuation of Jardiance. 2, 7
• Surgical procedures or prolonged fasting: Jardiance must be withheld at least 3–4 days before scheduled surgery to prevent postoperative ketoacidosis. 2, 8, 4
• Reduction or cessation of insulin doses in insulin-requiring patients while continuing SGLT2 inhibitors creates a critical metabolic environment for DKA. 7, 9
• Low-carbohydrate or ketogenic diets combined with SGLT2 inhibitors dramatically increase DKA risk, as demonstrated by case reports of severe ketoacidosis in patients on both empagliflozin and ketogenic diets. 9
• Critical illness or hospitalization requires immediate discontinuation of Jardiance due to volume depletion and metabolic stress. 7, 6

Immediate Management Algorithm When DKA Is Suspected

• Stop Jardiance immediately if any signs of DKA develop (nausea, vomiting, abdominal pain, dyspnea, malaise) regardless of blood glucose level. 2, 7
• Check blood or urine ketones and arterial blood gases in any patient on SGLT2 inhibitors presenting with these symptoms, even if glucose is normal or only mildly elevated. 3, 6
• Initiate standard DKA protocol with intravenous hydration and insulin infusion; do not restart Jardiance until DKA has fully resolved and precipitating factors are addressed. 3, 4
• Maintain at least low-dose insulin in insulin-requiring patients even when Jardiance is held, as complete insulin cessation compounds DKA risk. 7

Critical Pitfall: Prolonged Drug Effect After Discontinuation

• Jardiance can cause persistent glucosuria and ketonuria for up to 11 days after the last dose, with documented cases of DKA relapse occurring 8 days after drug cessation due to ongoing SGLT2 inhibition. 4
• This prolonged effect means patients remain at risk for recurrent euglycemic DKA even after stopping the medication, requiring extended monitoring and maintenance of adequate carbohydrate intake during recovery. 4

Patient Education to Prevent DKA

• Counsel patients to stop Jardiance immediately when they become sick and cannot maintain normal oral intake, and to contact their healthcare provider. 7
• Instruct patients to seek immediate medical attention if they develop nausea, vomiting, abdominal pain, dyspnea, or malaise, even if home glucose readings are normal. 7, 3
• Educate patients on sick-day planning: discontinue Jardiance during fever, vomiting, diarrhea, or any intercurrent illness requiring hospitalization. 7
• Warn patients explicitly about the risk of euglycemic DKA—that dangerous ketoacidosis can occur even with normal blood glucose levels. 2, 7

When to Permanently Discontinue Jardiance

• Permanent cessation is mandatory after any episode of DKA attributed to SGLT2 inhibitor use, as documented in multiple case reports where empagliflozin or dapagliflozin was discontinued indefinitely following euglycemic DKA. 3, 9, 6
• Patients with recurrent DKA episodes, those unable to maintain adequate carbohydrate intake, or those on ketogenic diets should not be prescribed SGLT2 inhibitors. 9