Yes, Jardiance (empagliflozin) can cause ketones in the urine, including in the setting of euglycemic diabetic ketoacidosis.
Jardiance and other SGLT2 inhibitors are associated with ketonuria and the serious risk of diabetic ketoacidosis, which can occur even when blood glucose levels are normal or only mildly elevated (euglycemic DKA). This is a well-documented adverse effect that requires awareness and appropriate risk mitigation 1.
Mechanism of Ketonuria with SGLT2 Inhibitors
SGLT2 inhibitors like Jardiance cause ketonuria through multiple mechanisms 2:
- Enhanced lipolysis and ketone production: Increased glucagon levels and decreased insulin effect promote fat breakdown and ketogenesis
- Decreased renal clearance of ketones: SGLT2 inhibition reduces urinary excretion of ketone bodies
- Increased glycosuria: The medication eliminates 60-100 g of glucose daily through urine, creating a relative carbohydrate-depleted state that favors ketone production
The FDA drug label explicitly warns that ketoacidosis with increased ketones in blood or urine has been reported in patients taking Jardiance, and this can occur even when blood glucose is less than 250 mg/dL 1.
Clinical Significance and Risk Factors
The presence of ketonuria in patients on Jardiance ranges from benign to life-threatening 3, 4, 5:
High-risk situations for ketoacidosis include 2, 3, 2:
- Insulin deficiency or significant insulin dose reduction
- Surgery or trauma (discontinue 3-4 days before elective procedures)
- Prolonged fasting or severe carbohydrate restriction
- Acute illness, infection, or volume depletion
- Alcohol abuse
- Pancreatic disorders
Monitoring and Management Approach
If a patient on Jardiance develops symptoms of nausea, vomiting, abdominal pain, tiredness, or trouble breathing, check for ketones in the urine even if blood glucose is normal 1. The FDA label specifically instructs patients to check urine ketones if these symptoms occur.
Key Clinical Pearls:
Persistent ketonuria and glucosuria can occur for 7-12 days after the last dose of empagliflozin, even when serum glucose is below the renal threshold 6, 7. This prolonged effect is due to the drug's mechanism of action, not just its half-life.
Euglycemic DKA can recur during this washout period if precipitating factors persist 6, 7
The FDA label notes that "elevated glucose in urinalysis is expected when taking Jardiance" 1, so glucosuria alone is not concerning, but the combination of glucosuria with ketonuria warrants evaluation
Prevention Strategies
To minimize ketoacidosis risk while on Jardiance 3, 8, 9:
- Institute sick-day protocols: Hold the medication during acute illness, reduced oral intake, or volume depletion
- Discontinue 3-4 days before scheduled surgery 3, 10, 9
- Maintain at least low-dose insulin in insulin-requiring patients 8
- Educate patients on signs/symptoms of ketoacidosis and when to check ketones
- Avoid in patients with type 1 diabetes (not FDA-approved for this indication due to increased ketoacidosis risk) 1
Common Pitfall:
The normal or mildly elevated glucose levels in euglycemic DKA can delay recognition and treatment. Always maintain high clinical suspicion for ketoacidosis in symptomatic patients on SGLT2 inhibitors, regardless of glucose level 11, 12, 13.