What are the risks of diabetic ketoacidosis (DKA) associated with Jardiance (Empagliflozin) in patients with type 2 diabetes?

Jardiance and Diabetic Ketoacidosis Risk

Jardiance (empagliflozin) carries a real but uncommon risk of diabetic ketoacidosis in type 2 diabetes patients, with an incidence of 0.6-4.9 events per 1,000 person-years, and critically, this can present as euglycemic DKA with blood glucose levels below 250 mg/dL in up to 71% of cases. 1

Absolute Contraindications

Do not use Jardiance in patients with: 2

• History of prior diabetic ketoacidosis
• Type 1 diabetes
• Severe renal impairment (eGFR <30 mL/min/1.73 m²)
• Known hypersensitivity to empagliflozin

Risk Magnitude and Clinical Context

The DKA risk with SGLT2 inhibitors in type 2 diabetes is significantly lower than in type 1 diabetes (where it occurs in ~4% of patients, with 5-17 times higher risk). 1 However, the relative risk in type 2 diabetes is still elevated at 2.46 compared to placebo or active comparators. 1

The critical clinical pitfall: Up to one-third of SGLT2 inhibitor-associated DKA cases present with glucose <200 mg/dL, and 71% present with glucose ≤250 mg/dL. 1 This euglycemic presentation delays recognition and treatment, making it particularly dangerous. 2, 3, 4

High-Risk Situations Requiring Jardiance Discontinuation

Temporarily discontinue Jardiance during: 1, 5, 2

• Prolonged fasting or acute illness with reduced oral intake
• Surgical procedures (stop 3-4 days before scheduled surgery)
• Acute febrile illness or infection
• Volume depletion states
• Excessive alcohol consumption or binge drinking

Exercise extreme caution in: 1, 5

• Insulin-deficient states (low C-peptide, history of pancreatitis or pancreatic surgery)
• Very-low-carbohydrate or ketogenic diets
• Elderly patients with multiple comorbidities
• Patients on concurrent diuretics
• Patients with low baseline systolic blood pressure
• Reduced renal function (though not contraindicated until eGFR <30)

Patient Education Requirements

Before prescribing Jardiance, educate patients to: 1, 2

• Recognize DKA symptoms: nausea, vomiting, abdominal pain, weakness, shortness of breath, generalized malaise
• Understand that DKA can occur even with "normal" blood sugar readings (150-250 mg/dL range)
• Check urine or blood ketones when experiencing these symptoms, regardless of glucose level
• Seek immediate medical attention if DKA symptoms develop
• Hold medication during acute illness with poor oral intake
• Avoid prolonged fasting while on therapy

Monitoring Strategy

At initiation: 1, 2

• Assess volume status and correct depletion before starting
• Verify eGFR ≥45 mL/min/1.73 m² (do not initiate if lower)
• Screen for insulin deficiency risk factors (pancreatic disease history, autoantibodies in unclear diabetes type)

During treatment: 1, 2

• Monitor for dehydration symptoms (lightheadedness, orthostasis, weakness)
• Periodic renal function assessment
• Discontinue if eGFR persistently <45 mL/min/1.73 m²
• Increase monitoring frequency during intercurrent illness

Management of Suspected DKA

If DKA is suspected: 1, 2

• Check ketones (blood or urine) immediately, even if glucose <250 mg/dL
• Assess acid-base status and electrolytes
• Discontinue Jardiance permanently if DKA confirmed
• Initiate standard DKA protocol (insulin infusion, fluid resuscitation, electrolyte replacement)
• Do not restart SGLT2 inhibitors after a DKA episode

Risk-Benefit Considerations

Despite the DKA risk, Jardiance provides substantial cardiovascular and renal benefits in appropriate patients with type 2 diabetes. 5, 2 The key is proper patient selection, avoiding use in high-risk scenarios, and ensuring comprehensive patient education about warning signs. 1

The most common error: Failing to recognize euglycemic DKA because glucose levels don't meet traditional DKA thresholds (>250 mg/dL). 1, 3 Always check ketones in symptomatic patients on SGLT2 inhibitors regardless of glucose level.