In a 65-year-old woman with type 2 diabetes on empagliflozin (Jardiance), metformin, and sitagliptin, does a ketone level of 0.9 mmol/L with a blood glucose of 104 mg/dL indicate euglycemic diabetic ketoacidosis and what management steps are recommended?

Immediate Management of Ketones 0.9 mmol/L with Blood Glucose 104 mg/dL in a Patient on Jardiance

Stop Jardiance immediately—this presentation indicates euglycemic diabetic ketoacidosis (euDKA), a life-threatening complication of SGLT2 inhibitors that can progress rapidly even with normal blood glucose levels. 1, 2

Diagnostic Confirmation

• Measure serum β-hydroxybutyrate urgently; a level ≥ 0.6 mmol/L confirms ketosis, and ≥ 3.0 mmol/L confirms diabetic ketoacidosis regardless of glucose concentration. 3
• Obtain venous blood gas or basic metabolic panel to assess for anion gap metabolic acidosis (anion gap > 12 mmol/L supports DKA diagnosis). 3
• Check serum bicarbonate; levels < 18 mmol/L with elevated ketones and anion gap confirm DKA. 2
• A ketone level of 0.9 mmol/L with glucose 104 mg/dL in an SGLT2-inhibitor user represents moderate ketosis that warrants immediate intervention, as euglycemic DKA can present with minimal symptoms initially but deteriorate rapidly. 1, 4, 5

Immediate Clinical Actions

• Discontinue Jardiance (empagliflozin) permanently—do not restart even after resolution, as recurrence risk remains high. 1, 2
• Assess for precipitating factors: reduced oral intake, acute illness (fever, vomiting, diarrhea, urinary tract infection), recent surgery, or alcohol use. 1, 2, 5
• Evaluate volume status clinically; signs of dehydration (dry mucous membranes, decreased skin turgor, orthostatic hypotension) indicate need for aggressive fluid resuscitation. 2, 6
• Check for DKA symptoms even if patient reports feeling well: nausea, vomiting, abdominal pain, dyspnea, malaise, or confusion—these may be subtle or absent in euglycemic DKA. 1, 4, 5

Hospital Admission Criteria

• Admit to hospital for intravenous insulin and fluid therapy if any of the following are present:
  • Serum bicarbonate < 18 mmol/L 2
  • Anion gap > 12 mmol/L 3
  • β-hydroxybutyrate ≥ 3.0 mmol/L 3
  • Symptoms of DKA (nausea, vomiting, abdominal pain, dyspnea) 1, 5
  • Inability to maintain oral hydration 1

Inpatient DKA Management (if criteria met)

• Start intravenous insulin infusion at 0.1 units/kg/hour even with normal glucose; continue until ketones clear and anion gap closes. 1, 2
• Administer isotonic saline (0.9% NaCl) at 15–20 mL/kg/hour initially (approximately 1–1.5 L in first hour) to correct volume depletion. 2
• Add dextrose-containing fluids (D5W or D10W) when glucose falls below 200 mg/dL to prevent hypoglycemia while continuing insulin to clear ketones. 1, 2
• Replace potassium aggressively; add 20–40 mEq/L to IV fluids once serum potassium < 5.3 mEq/L and urine output is adequate. 2
• Monitor β-hydroxybutyrate every 2–4 hours; resolution is defined as β-hydroxybutyrate < 0.6 mmol/L and closure of anion gap. 3

Outpatient Management (if DKA excluded but ketosis present)

• If serum bicarbonate ≥ 18 mmol/L, anion gap ≤ 12 mmol/L, and patient is asymptomatic, outpatient management may be appropriate with close follow-up. 3
• Increase oral fluid intake to at least 2–3 liters daily to promote ketone clearance. 1
• Initiate or increase basal insulin (e.g., glargine 10 units once daily or 0.2 units/kg) to suppress ketogenesis; titrate by 2–4 units every 3 days until fasting glucose 80–130 mg/dL. 3, 7
• Continue metformin at current dose (assuming eGFR ≥ 30 mL/min/1.73 m²) for insulin-sparing effect and cardiovascular benefit. 3
• Temporarily hold sitagliptin until ketones resolve, then resume at usual dose. 3
• Recheck β-hydroxybutyrate or urine ketones in 24–48 hours; if ketones persist or worsen, admit for IV insulin therapy. 1, 7

Medication Adjustments After Resolution

• Do not restart Jardiance; the risk of recurrent euglycemic DKA remains unacceptably high. 1, 2
• Optimize basal insulin as primary glucose-lowering agent; target fasting glucose 80–130 mg/dL. 3
• Consider adding a GLP-1 receptor agonist (e.g., semaglutide, titrated to 1 mg weekly) if HbA1c remains > 7% after 3 months of optimized metformin + basal insulin. 3
• Resume metformin and sitagliptin once ketones have cleared and patient is eating normally. 3

Patient Education & Sick-Day Rules

• Educate that SGLT2 inhibitors must be stopped during any illness with reduced oral intake, fever, vomiting, or diarrhea—even if glucose is normal. 1, 2
• Warn that dangerous ketoacidosis can develop despite normal blood glucose while on Jardiance. 1, 2
• Instruct to seek urgent medical evaluation for nausea, vomiting, abdominal pain, dyspnea, or malaise even if home glucose readings are normal. 1, 5
• Emphasize that Jardiance should have been stopped at least 3–4 days before any planned surgery or prolonged fasting. 1, 2

Common Pitfalls to Avoid

• Do not dismiss ketones of 0.9 mmol/L as "mild" in an SGLT2-inhibitor user—this represents significant ketogenesis that can rapidly progress to full DKA. 1, 4, 5
• Do not wait for hyperglycemia to diagnose DKA; euglycemic DKA is the hallmark complication of SGLT2 inhibitors and requires immediate treatment. 1, 2, 4
• Do not restart Jardiance after resolution; the mechanism of SGLT2-inhibitor-induced ketogenesis persists and recurrence is common. 1, 7
• Do not stop insulin prematurely; ketones may persist for days beyond the expected half-life of empagliflozin (12.9 hours), requiring continued basal insulin until complete resolution. 7
• Do not overlook volume depletion; the combination of SGLT2-inhibitor diuresis and reduced oral intake creates a high-risk metabolic state. 2, 6, 5

Long-Term Glycemic Strategy

• Basal insulin + metformin + sitagliptin provides effective glucose control without DKA risk. 3
• Target HbA1c < 7% in this 65-year-old without established complications. 3
• Monitor HbA1c every 3 months until target achieved, then every 6 months. 3
• If cardiovascular or renal protection is needed, consider switching to a GLP-1 receptor agonist rather than restarting an SGLT2 inhibitor, as GLP-1 RAs provide similar cardiovascular benefits without ketoacidosis risk. 3