In a hyperglycemic patient with elevated blood glucose and ketonuria, should I hold Jardiance (empagliflozin)?

Yes, Hold Jardiance Immediately

In a hyperglycemic patient with ketonuria, you must discontinue Jardiance (empagliflozin) immediately and assess for diabetic ketoacidosis (DKA), regardless of the blood glucose level.

Why This Is Critical

SGLT2 inhibitors like Jardiance carry a serious risk of ketoacidosis, including euglycemic DKA where ketoacidosis occurs even with blood glucose levels below 250 mg/dL 1. The FDA label explicitly warns that ketoacidosis associated with SGLT2 inhibitors may be present even with blood glucose less than 250 mg/dL, and if ketoacidosis is suspected, the drug should be discontinued immediately 1.

The presence of both hyperglycemia AND ketonuria in your patient represents a clear warning sign that should trigger immediate action.

Immediate Clinical Actions

Assess for DKA now:

• Check blood β-hydroxybutyrate (preferred) or serum/urine ketones
• Obtain venous blood gas or arterial blood gas to assess pH and anion gap
• Look for signs/symptoms: nausea, vomiting, abdominal pain, shortness of breath, generalized malaise 1
• Remember: the patient may appear relatively well despite significant ketoacidosis

If DKA is confirmed:

• Discontinue Jardiance permanently for this episode
• Initiate standard DKA treatment: IV fluids, insulin infusion, electrolyte replacement 2
• Do NOT restart Jardiance until ketoacidosis has fully resolved and precipitating factors are addressed 1

Key Guideline Support

The KDIGO 2020 guidelines explicitly state: "It is reasonable to withhold SGLT2i during times of prolonged fasting, surgery, or critical medical illness (when patients may be at greater risk for ketosis)" 3. Your patient's presentation with hyperglycemia and ketonuria qualifies as a critical situation requiring drug discontinuation.

The 2023 consensus on sick day medication guidance recommends temporarily stopping SGLT2 inhibitors when patients have symptoms suggesting volume depletion or metabolic decompensation 4. The presence of ketonuria is a red flag that metabolic decompensation may be occurring.

Common Pitfall to Avoid

Do not be falsely reassured by "only moderate" hyperglycemia. The most dangerous aspect of SGLT2i-associated DKA is that it frequently presents with blood glucose levels that seem "not that high" (often <250 mg/dL), leading to delayed recognition and treatment 1. In postmarketing reports, delayed recognition due to lower-than-expected glucose levels was a recurring theme, particularly problematic because clinicians weren't looking for DKA 1.

Risk Factors Present

Your patient likely has one or more precipitating factors:

• Acute illness or infection
• Reduced caloric intake
• Dehydration
• Insulin deficiency (relative or absolute)
• Recent surgery or fasting 1

When to Consider Restarting

Only restart Jardiance after:

1. Complete resolution of ketoacidosis (pH normalized, ketones cleared)
2. Identification and resolution of precipitating factors
3. Patient is eating and drinking normally
4. Careful risk-benefit reassessment 1

For many patients who develop SGLT2i-associated DKA, permanent discontinuation may be the safest approach, particularly if insulin deficiency or recurrent risk factors are present 1.

Bottom Line Algorithm

Patient on Jardiance + hyperglycemia + ketonuria:

1. Stop Jardiance immediately
2. Check blood β-hydroxybutyrate and venous pH
3. If ketones elevated (>0.6 mmol/L) or pH <7.3 → treat as DKA
4. If ketones normal and pH normal → investigate other causes but keep Jardiance held until clinical picture clarifies
5. Do not restart until complete metabolic recovery and risk factors resolved