What is the role of Empagliflozin (Jardiance) in the treatment of type 2 diabetes?

Role of Empagliflozin in Type 2 Diabetes Management

Empagliflozin (Jardiance) is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that should be prioritized as a second-line agent after metformin in patients with type 2 diabetes who have established cardiovascular disease, heart failure, or chronic kidney disease due to its proven cardiovascular and renal benefits.

Mechanism of Action and Indications

Empagliflozin works by inhibiting SGLT2 in the proximal renal tubules, reducing glucose reabsorption and increasing urinary glucose excretion. It is FDA-approved for:

• Improving glycemic control in adults with type 2 diabetes as an adjunct to diet and exercise
• Reducing the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease 1

Glycemic Efficacy

• Reduces HbA1c by approximately 0.7-1.0% when used as monotherapy or add-on therapy 2
• Efficacy is maintained over time as its mechanism is independent of insulin production 3
• Efficacy decreases in patients with declining renal function (eGFR <45 ml/min/1.73 m²) 4

Cardiovascular Benefits

Empagliflozin demonstrates significant cardiovascular protection:

• In the EMPA-REG OUTCOME trial, empagliflozin reduced:

  • Major adverse cardiovascular events (MACE) by 14% (HR 0.86; 95% CI 0.74-0.99) 5, 6
  • Cardiovascular death by 38% (HR 0.62; 95% CI 0.49-0.77) 5, 6
  • All-cause mortality by 32% (HR 0.68; 95% CI 0.57-0.82) 6
  • Hospitalization for heart failure by 35% 5

• Benefits extend to patients with heart failure with preserved ejection fraction (HFpEF), showing a 21% reduction in the composite outcome of cardiovascular death or hospitalization for heart failure 5

Renal Benefits

Empagliflozin offers significant renoprotection:

• Reduces the risk of incident or worsening nephropathy by 39% (HR 0.61; 95% CI 0.53-0.70) 7
• Decreases the risk of doubling of serum creatinine by 44% 7
• Reduces the need for renal replacement therapy by 55% 7
• May cause an initial, hemodynamically-mediated decrease in eGFR that is typically reversible 2

Patient Selection and Positioning in Therapy

1. First-line therapy: Metformin remains the first-line agent for most patients with type 2 diabetes 2

2. Second-line therapy:

   • For patients with established ASCVD, heart failure, or CKD: Add empagliflozin 2
   • For patients needing greater weight loss: Consider GLP-1 receptor agonists 2
   • For patients with cost concerns: Consider sulfonylureas 2

3. Special populations:

   • Youth with type 2 diabetes: Empagliflozin is now approved for use in children aged 10-17 years with type 2 diabetes, showing significant A1C reduction compared to placebo 5
   • Patients with renal impairment: Effective until eGFR ≥45 ml/min/1.73 m² 3

Safety Considerations

• Low hypoglycemia risk when used as monotherapy, but risk increases when combined with insulin or sulfonylureas 2, 3
• Genital mycotic infections: More common, especially in women, but typically mild and manageable 3
• Volume depletion: Generally not clinically significant in patients under 60 years but requires caution in elderly or frail patients 3
• Contraindications: Not recommended for type 1 diabetes or treatment of diabetic ketoacidosis 1
• Drug interactions: Minimal clinically significant interactions with other medications 3

Dosing and Administration

• Simple once-daily oral dosing 3
• Starting dose: 10 mg once daily
• Can be increased to 25 mg once daily if needed and tolerated
• Consider reducing doses of insulin or sulfonylureas by 20-50% when adding empagliflozin to prevent hypoglycemia 2
• Monitor renal function, particularly in the first several weeks of therapy 2

Practical Considerations

• Empagliflozin promotes weight loss and blood pressure reduction as additional benefits 3
• Unlike some other SGLT2 inhibitors (e.g., canagliflozin), empagliflozin has not been associated with increased risk of amputation or bone fractures 8
• Discontinue if eGFR falls below 45 ml/min/1.73 m² 3

Empagliflozin represents a significant advancement in type 2 diabetes management, offering benefits beyond glycemic control that directly impact morbidity and mortality outcomes.