What is the role of Jardiance (empagliflozin) in protecting against major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease?

Jardiance (Empagliflozin) for Cardiovascular Protection in Type 2 Diabetes

Jardiance (empagliflozin) significantly reduces the risk of cardiovascular death by 38% and major adverse cardiovascular events by 14% in adults with type 2 diabetes and established cardiovascular disease. 1, 2

Mechanism and Cardiovascular Benefits

Empagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that has demonstrated substantial cardiovascular protective effects beyond its glucose-lowering action. The EMPA-REG OUTCOME trial provided definitive evidence of its cardiovascular benefits:

• Primary composite outcome reduction: 14% reduction in major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) 2
• Cardiovascular mortality reduction: 38% reduction in cardiovascular death (absolute rate 3.7% vs. 5.9% in placebo) 2
• Heart failure hospitalization reduction: 35% reduction 2
• All-cause mortality reduction: 32% reduction 2

FDA-Approved Cardiovascular Indication

The FDA has specifically approved empagliflozin to:

• Reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease 2, 1

Patient Selection for Cardiovascular Protection

Empagliflozin should be prioritized for patients with:

1. Type 2 diabetes with established atherosclerotic cardiovascular disease 2
2. Inadequately controlled type 2 diabetes (HbA1c ≥7.0%) 1
3. Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m² 2

Dosing for Cardiovascular Protection

• Starting dose: 10 mg once daily 2
• No dose titration is needed specifically for cardiovascular risk reduction 2
• Dose increases to 25 mg daily may provide additional glucose-lowering benefits but are not necessary for cardiovascular protection 2

Special Populations and Cardiovascular Benefits

The cardiovascular benefits of empagliflozin extend to important subgroups:

• Chronic kidney disease: Patients with eGFR <60 mL/min/1.73 m² still derive cardiovascular benefits 3
• Heart failure: Significant reduction in heart failure hospitalizations regardless of baseline ejection fraction 1
• Age: Benefits consistent across age groups, including those ≥75 years 1

Important Cautions and Contraindications

Empagliflozin is contraindicated in:

• Patients on dialysis 2
• Patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) 2

Exercise caution with:

• Risk of volume depletion: Consider reducing diuretic doses when initiating 2
• Risk of euglycemic diabetic ketoacidosis 2
• Discontinue at least 3 days before planned surgery to prevent postoperative ketoacidosis 2

Monitoring Recommendations

• Renal function: Monitor eGFR, particularly in patients with baseline renal impairment
• Signs of genital mycotic infections and urinary tract infections
• Symptoms of diabetic ketoacidosis, even with normal blood glucose levels
• Volume status, especially when used with diuretics

Algorithm for Use in Clinical Practice

1. Identify eligible patients: Type 2 diabetes with established cardiovascular disease
2. Assess renal function: Confirm eGFR ≥30 mL/min/1.73 m²
3. Evaluate current medications: Consider reducing diuretic doses if applicable
4. Initiate empagliflozin 10 mg daily: This dose is sufficient for cardiovascular protection
5. Monitor for adverse effects: Particularly genital infections, volume depletion, and ketoacidosis
6. Continue indefinitely: The cardiovascular benefits appear to persist with ongoing treatment

Conclusion

Empagliflozin represents a significant advancement in reducing cardiovascular morbidity and mortality in patients with type 2 diabetes and established cardiovascular disease. Its benefits extend beyond glucose control to provide meaningful reductions in cardiovascular death, heart failure hospitalizations, and all-cause mortality.