Features of DKA in Patients Taking Jardiance (Empagliflozin)
The most critical feature of DKA in patients taking Jardiance is that it presents as euglycemic ketoacidosis—meaning severe metabolic acidosis with ketosis occurs despite blood glucose levels often below 250 mg/dL, which delays recognition and treatment. 1
Key Clinical Presentation
Atypical Glucose Levels
- Blood glucose is typically <250 mg/dL (often 150-200 mg/dL range), which is below the threshold clinicians expect for classic DKA 1
- This euglycemic presentation is the defining characteristic that makes diagnosis challenging and dangerous
- Cases have been reported with glucose as low as 168-185 mg/dL 2, 3, 4
Classic Metabolic Acidosis Features
Despite lower glucose, the metabolic derangement is severe:
- Severe metabolic acidosis with pH often <7.1 1, 3
- Elevated anion gap (typically >20-30 mmol/L) 2, 3
- Markedly elevated beta-hydroxybutyrate (>3-7 mmol/L) 2, 3
- Low bicarbonate (<10-15 mmol/L) 2, 3
- Positive urine ketones (4+) and glucosuria 3, 4
Presenting Symptoms
The FDA label and recent guidelines identify these symptoms 1, 5:
- Nausea and vomiting
- Abdominal pain
- Generalized malaise and weakness
- Shortness of breath
- Signs of dehydration
Critical pitfall: These symptoms mimic many acute illnesses, and the normal-range glucose leads clinicians to miss the diagnosis of DKA.
High-Risk Precipitating Factors
The FDA label specifically warns about these triggers 1:
Insulin Deficiency States
- Missed or reduced insulin doses
- Pancreatic disorders (pancreatitis, pancreatic surgery)
- Type 1 diabetes (though Jardiance is contraindicated in T1DM)
- Unrecognized autoimmune diabetes
Metabolic Stressors
- Acute febrile illness (influenza, COVID-19) 2, 3
- Surgery or trauma 1, 6
- Prolonged fasting or reduced caloric intake 1, 7
- Ketogenic or very low-carbohydrate diets 2, 7—particularly dangerous as SGLT2i eliminates 60-100g glucose/day 5
- Alcohol abuse 1
- Volume depletion 5
Timing Considerations
- Can occur within 48-72 hours of starting empagliflozin 2—not just after prolonged use
- May persist or recur for 7-14 days after last dose due to persistent glucosuria and ketonuria 4
Pathophysiology Unique to SGLT2 Inhibitors
The mechanism differs from classic DKA 5:
- Enhanced glycosuria (forced urinary glucose loss)
- Increased lipolysis and ketone production
- Hyperglucagonemia driving gluconeogenesis
- Decreased renal excretion of ketone bodies—ketones accumulate despite glucose loss
- The glucose-lowering effect masks the severity of metabolic decompensation
Management Implications
Immediate Recognition
Assess for ketoacidosis in ANY patient on Jardiance presenting with metabolic acidosis symptoms, regardless of blood glucose level 1
- Check beta-hydroxybutyrate or urine ketones immediately
- Obtain venous or arterial blood gas
- Calculate anion gap
Treatment Approach
Once diagnosed 1:
- Discontinue Jardiance immediately
- Standard DKA protocol: IV insulin infusion, aggressive fluid resuscitation, electrolyte replacement
- Add dextrose earlier than classic DKA since glucose is already low
- Monitor for recurrence up to 2 weeks after last dose 4
Prevention Strategy
The FDA label mandates 1:
- Discontinue Jardiance at least 3 days before scheduled surgery
- Consider temporary discontinuation during acute illness, prolonged fasting, or other high-risk situations
- Educate patients on warning signs and instruct them to stop medication and seek immediate care if symptoms develop
- Reassess diabetes phenotype if insulin requirements are unexpectedly low 2
Critical Clinical Pearls
- The normal glucose is the trap—don't rule out DKA based on glucose <250 mg/dL in SGLT2i users 1
- Persistent glucosuria (4+) with ketonuria (4+) confirms ongoing SGLT2i effect even days after discontinuation 4
- Fatal cases have been reported, making early recognition life-saving 1
- This can occur in both type 1 and type 2 diabetes, and even rarely in non-diabetic patients on SGLT2i for heart failure 8