Indications and Usage of Jardiance (Empagliflozin) in Type 2 Diabetes
Jardiance (empagliflozin) is indicated to improve glycemic control in adults with type 2 diabetes as an adjunct to diet and exercise, and to reduce cardiovascular death in adults with type 2 diabetes and established cardiovascular disease. 1, 2
Primary Indications
Jardiance has multiple FDA-approved indications:
Glycemic control: To improve glycemic control in adults with type 2 diabetes as an adjunct to diet and exercise 1, 2
Cardiovascular risk reduction: To reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease 1
Heart failure management: To reduce the risk of hospitalization for heart failure in adults with heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) 1
Renal protection: To reduce the risk of end-stage kidney disease, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in patients with type 2 diabetes and diabetic nephropathy with albuminuria 1
Dosing and Administration
- Starting dose: 10 mg orally once daily, taken in the morning 1, 2
- Maximum dose: 25 mg orally once daily 1, 2
- Renal dose adjustments:
- eGFR 30-59 ml/min/1.73 m²: No dose adjustment needed
- eGFR <45 ml/min/1.73 m²: Not recommended for glycemic control
- eGFR <30 ml/min/1.73 m²: Not recommended 1
Clinical Evidence Supporting Indications
Cardiovascular Benefits
The EMPA-REG OUTCOME trial demonstrated that empagliflozin significantly reduced:
- Composite outcome of MI, stroke, and cardiovascular death by 14% (HR 0.86 [95% CI 0.74-0.99]) 1
- Cardiovascular death by 38% (HR 0.62 [95% CI 0.49-0.77]) 1
- Hospitalization for heart failure by 35% 1
Renal Benefits
Empagliflozin showed significant renoprotective effects:
- 44% reduction in doubling of serum creatinine 3
- 55% reduction in initiation of renal replacement therapy 3
- 39% reduction in incident or worsening nephropathy 1
Glycemic Control
In clinical trials, empagliflozin demonstrated:
- HbA1c reduction of 0.7-0.8% as monotherapy compared to placebo 2
- Similar efficacy across various patient subgroups regardless of age, sex, race, BMI, or diabetes duration 2
Place in Therapy
According to current guidelines:
First-line therapy: Metformin remains first-line therapy for most patients with type 2 diabetes 1
Second-line therapy: For patients with established ASCVD, heart failure, or CKD, an SGLT2 inhibitor with demonstrated cardiovascular benefit (such as empagliflozin) is recommended as part of the glucose-lowering regimen independent of A1C and independent of metformin use 1
Preferred populations:
- Patients with established cardiovascular disease
- Patients with heart failure (particularly HFrEF)
- Patients with chronic kidney disease with albuminuria
- Patients with multiple cardiovascular risk factors 1
Safety Considerations
Common adverse effects include:
- Genital fungal infections
- Urinary tract infections
- Volume depletion (particularly in elderly or those on diuretics)
- Euglycemic diabetic ketoacidosis (rare but serious) 1
Important precautions:
- Discontinue at least 3 days before scheduled surgery to prevent postoperative ketoacidosis
- Use with caution in patients with renal impairment
- Consider reducing insulin dose by ~20% when initiating therapy to prevent hypoglycemia
- May contribute to intravascular volume contraction; consider reducing diuretic doses if applicable 1
Key Differentiators from Other SGLT2 Inhibitors
Unlike canagliflozin (another SGLT2 inhibitor with cardiovascular benefits), empagliflozin has not been associated with increased risk of lower limb amputations 4, making it a potentially safer option for patients with peripheral vascular disease.
Empagliflozin was the first SGLT2 inhibitor to demonstrate cardiovascular mortality benefit in a dedicated cardiovascular outcomes trial, establishing its role as a preferred agent for patients with type 2 diabetes and established cardiovascular disease 1, 4.