What is the indication for Jardiance (empagliflozin) in adults with type 2 diabetes mellitus, particularly those with established cardiovascular disease or at high risk for cardiovascular events and impaired renal function?

Indications for Jardiance (Empagliflozin)

Jardiance is FDA-approved for two primary indications: improving glycemic control in adults with type 2 diabetes mellitus as an adjunct to diet and exercise, and reducing the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease. 1

FDA-Approved Indications

Glycemic Control

• Jardiance is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus 1
• The recommended starting dose is 10 mg once daily, taken in the morning, with or without food 1
• The dose may be increased to 25 mg once daily for additional glucose-lowering benefit if needed, though no additional cardiovascular protection is gained from the higher dose 2

Cardiovascular Risk Reduction

• Jardiance is specifically indicated to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease 1, 2
• This indication stems from the EMPA-REG OUTCOME trial, which demonstrated a 38% reduction in cardiovascular death (HR 0.62,95% CI 0.49-0.77) in patients with type 2 diabetes and existing cardiovascular disease 2
• The trial also showed a 14% reduction in the composite outcome of MI, stroke, and cardiovascular death 2

Guideline-Recommended Indications Beyond FDA Label

Heart Failure Risk Reduction

• The European Society of Cardiology and American Diabetes Association recommend empagliflozin to lower the risk of heart failure hospitalization in patients with type 2 diabetes and cardiovascular disease or at very high/high cardiovascular risk 2
• Empagliflozin reduced heart failure hospitalization by 39% (HR 0.61,95% CI 0.42-0.87) in patients with prevalent kidney disease and established cardiovascular disease 3

Renal Protection

• SGLT2 inhibitors including empagliflozin are recommended to reduce progression of diabetic kidney disease 2
• Empagliflozin reduced incident or worsening nephropathy by 39% (HR 0.61,95% CI 0.53-0.70) and decreased the risk of doubling serum creatinine by 44% 4
• These renal benefits were observed even in patients with chronic kidney disease (eGFR <60 mL/min/1.73 m²) at baseline 3

Mortality Reduction

• Empagliflozin is recommended specifically to reduce the risk of death in patients with type 2 diabetes and cardiovascular disease 2
• All-cause mortality was reduced by 24% (HR 0.76,95% CI 0.59-0.99) in patients with prevalent kidney disease and established cardiovascular disease 3

Patient Selection Algorithm

Ideal Candidates for Empagliflozin

1. Patients with type 2 diabetes AND established cardiovascular disease (coronary artery disease, prior MI, stroke, or peripheral arterial disease) 2
2. Patients with type 2 diabetes at very high or high cardiovascular risk (multiple cardiovascular risk factors) 2
3. Patients with type 2 diabetes and chronic kidney disease (eGFR ≥30 mL/min/1.73 m² and/or albuminuria) 4, 3
4. Patients with type 2 diabetes at risk for heart failure 2

Renal Function Requirements

• Do not initiate Jardiance if eGFR is below 45 mL/min/1.73 m² for glycemic control purposes 1, 2
• Discontinue Jardiance if eGFR falls persistently below 45 mL/min/1.73 m² 1
• Jardiance is contraindicated in severe renal impairment, end-stage renal disease, or patients on dialysis 1, 2

Important Limitations and Contraindications

Absolute Contraindications

• History of serious hypersensitivity reaction to empagliflozin 1, 2
• Severe renal impairment, end-stage renal disease, or dialysis 1, 2

Not Indicated For

• Jardiance is not for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis 1

Common Pitfalls to Avoid

Dosing Errors

• Do not titrate empagliflozin beyond 10 mg daily solely for cardiovascular or renal protection, as there is no evidence of graded dose response for these outcomes 2
• The 10 mg dose tested in cardiovascular outcomes trials provides full cardiovascular and renal benefits 2, 5

Perioperative Management

• Discontinue empagliflozin at least 3 days before planned surgery to prevent postoperative ketoacidosis 2, 5

Concomitant Therapy Adjustments

• When initiating empagliflozin in patients on insulin or sulfonylureas, reduce the dose of these medications by approximately 20% for insulin or consider stopping sulfonylureas to prevent hypoglycemia 2, 5

Volume Status Considerations

• Before initiating empagliflozin, assess and correct volume status in patients with renal impairment, elderly patients, those with low systolic blood pressure, and patients on diuretics 1
• Consider stopping or reducing diuretic dose if volume depletion is a concern 2