Can Jardiance (empagliflozin) cause metabolic acidosis?

Can Jardiance Cause Metabolic Acidosis?

Yes, Jardiance (empagliflozin) can cause metabolic acidosis, specifically in the form of euglycemic diabetic ketoacidosis (euDKA), a serious and potentially life-threatening condition that requires urgent hospitalization. 1

Understanding the Risk

Empagliflozin carries an FDA black box-level warning for ketoacidosis, which presents as severe metabolic acidosis. 1 This condition is particularly dangerous because:

• Blood glucose levels are often normal or only mildly elevated (<250 mg/dL), making the diagnosis easily missed in emergency settings 2, 1
• Fatal cases have been reported in patients taking empagliflozin 1
• The condition can present with dehydration and severe metabolic acidosis including nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath 1

High-Risk Clinical Situations Requiring Drug Discontinuation

Stop empagliflozin immediately in these scenarios: 3, 2, 1

• Acute illness or infection 4, 2
• Reduced caloric intake due to illness or fasting 4, 2
• Surgical procedures (discontinue 3-4 days before elective surgery) 4, 2, 1
• Volume depletion or dehydration 2, 1
• Alcohol consumption 4, 2
• Any prolonged fasting state 1

Vulnerable Patient Populations

Exercise extreme caution or avoid empagliflozin in: 4, 2

• Patients with insulin deficiency (including type 1 diabetes—empagliflozin is NOT indicated for type 1 diabetes) 1, 5
• Elderly patients 3, 4
• Patients with reduced renal function 4, 1
• Patients on concurrent diuretics 3, 4
• Patients with low systolic blood pressure (<100 mmHg) 3, 2
• History of pancreatitis or pancreatic surgery 1

Mixed Metabolic Acidosis Pattern

Beyond ketoacidosis, empagliflozin can cause mixed metabolic acidosis with both ketoacidosis and hyperchloremic acidosis components due to complex renal metabolic dysfunction. 6 This mixed pattern can be particularly severe and has been associated with fatal outcomes in postoperative settings. 6

Immediate Management Protocol

If metabolic acidosis is suspected: 2, 1

1. Discontinue empagliflozin immediately 2, 1
2. Check blood or urine ketones regardless of glucose level 1
3. Initiate intravenous insulin infusion with dextrose-containing fluids 2
4. Provide aggressive fluid resuscitation 2
5. The condition typically resolves within 24 hours with appropriate management 2

Critical Patient Education

Counsel all patients taking empagliflozin to: 2

• Seek immediate medical attention if they develop nausea, vomiting, abdominal pain, or malaise 2
• Stop the medication during any acute illness 3, 2
• Follow "sick day rules" and discontinue during dehydration 3

Balancing Risk and Benefit

Despite this serious risk, empagliflozin offers substantial cardiovascular benefits including 38% reduction in cardiovascular death and 32% reduction in all-cause mortality in patients with type 2 diabetes and established cardiovascular disease. 7 The key is appropriate patient selection and vigilant monitoring for risk factors that predispose to ketoacidosis. 1