What is the role of Jardiance (empagliflozin) in treating type 2 diabetes?

Jardiance (Empagliflozin) for Type 2 Diabetes

Jardiance (empagliflozin) should be considered a preferred second-line agent after metformin for type 2 diabetes, particularly in patients with established cardiovascular disease, heart failure, or chronic kidney disease due to its proven cardiovascular and renal benefits.

Mechanism and Efficacy

Empagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that works by:

• Increasing urinary glucose excretion through an insulin-independent mechanism
• Providing moderate glycemic control (HbA1c reduction of 0.7-1.0%) 1
• Offering additional benefits beyond glucose lowering:
  • Modest weight reduction (2.1-2.5 kg) 2
  • Blood pressure reduction (2.9-5.2 mmHg systolic) 2

Cardiovascular Benefits

The landmark EMPA-REG OUTCOME trial demonstrated significant cardiovascular benefits in patients with type 2 diabetes and established cardiovascular disease 3:

• 14% reduction in major adverse cardiovascular events (MACE)
• 38% reduction in cardiovascular mortality
• 35% reduction in heart failure hospitalizations
• 32% reduction in all-cause mortality

These benefits were observed early in the trial, suggesting mechanisms beyond atherosclerosis reduction, likely related to hemodynamic effects 3.

Renal Benefits

Empagliflozin also demonstrates significant renoprotective effects:

• 39% reduction in progression of chronic kidney disease 3
• Benefits observed regardless of baseline HbA1c or glycemic control 3

Patient Selection and Dosing

Recommended for:

• Type 2 diabetes patients as an adjunct to diet and exercise 4
• Patients with established cardiovascular disease, heart failure (regardless of ejection fraction), or chronic kidney disease 1

Dosing:

• Starting dose: 10 mg once daily in the morning, with or without food 4
• May increase to 25 mg daily if tolerated 4

Renal Function Considerations:

• Assess renal function before initiation and periodically thereafter
• Do not initiate if eGFR <45 mL/min/1.73 m² 4
• Discontinue if eGFR persistently falls below 45 mL/min/1.73 m² 4

Contraindications

• History of serious hypersensitivity to empagliflozin
• Severe renal impairment (eGFR <30 mL/min/1.73 m²), end-stage renal disease, or dialysis 4
• Type 1 diabetes 4
• Pregnancy or breastfeeding 1

Adverse Effects and Monitoring

Common Adverse Effects:

• Genital mycotic infections
• Urinary tract infections
• Volume depletion (particularly in elderly or those on diuretics) 1

Rare but Serious Adverse Effects:

• Euglycemic diabetic ketoacidosis
• Hypotension due to intravascular volume contraction 4

Monitoring Recommendations:

• Renal function
• Signs of genital mycotic infections
• Volume status
• Symptoms of diabetic ketoacidosis
• Lower limb ulcerations 1

Special Considerations

• Consider correcting volume depletion prior to initiation 4
• May need to reduce dose of concurrent diuretics to prevent excessive volume depletion 1
• Discontinue at least 3 days before planned surgery to prevent postoperative ketoacidosis 1
• Use with caution in patients with peripheral vascular disease 1

Practical Implementation

For patients with type 2 diabetes:

1. Start with metformin as first-line therapy
2. Consider adding empagliflozin as second-line agent, especially if patient has:
   • Established cardiovascular disease
   • Heart failure (with reduced or preserved ejection fraction)
   • Chronic kidney disease (eGFR ≥45 mL/min/1.73 m²)
3. Monitor for adverse effects, particularly in the first few weeks of treatment
4. Counsel patients about symptoms of genital infections and volume depletion

Empagliflozin represents a significant advance in type 2 diabetes management, offering benefits beyond glycemic control that directly impact morbidity, mortality, and quality of life.