What is the use of Empagliflozin in type 2 diabetes mellitus?

Empagliflozin in Type 2 Diabetes Mellitus: Comprehensive Management

Empagliflozin is a first-line treatment for type 2 diabetes mellitus that not only improves glycemic control but significantly reduces cardiovascular mortality, heart failure hospitalizations, and slows progression of chronic kidney disease, making it an essential therapy for patients with type 2 diabetes, particularly those with established cardiovascular disease or multiple risk factors. 1

Mechanism and Glycemic Effects

• Empagliflozin (Jardiance®) is a potent, selective sodium-glucose cotransporter-2 (SGLT2) inhibitor that works by:
  • Inhibiting renal glucose reabsorption in the proximal tubule
  • Increasing urinary glucose excretion (64-78 grams per day)
  • Lowering blood glucose levels independent of insulin 2, 3
• Provides moderate A1C reduction of 0.7-1.0% 4
• Can be administered once daily with or without food 2

Cardiovascular Benefits

The EMPA-REG OUTCOME trial demonstrated that empagliflozin:

• Reduced the composite outcome of cardiovascular death, MI, or stroke by 14% (HR 0.86,95% CI 0.74-0.99) 1
• Decreased cardiovascular death by 38% (HR 0.62,95% CI 0.49-0.77) 1, 5
• Reduced all-cause mortality by 32% (HR 0.68,95% CI 0.57-0.82) 5
• Decreased hospitalization for heart failure by 35% 1

These benefits were observed within weeks of initiation and were consistent across different patient subgroups, including those with and without established heart failure 1, 4.

Renal Benefits

• Empagliflozin demonstrated significant renoprotective effects:
  • Slows decline in renal function in patients with type 2 diabetes 4
  • Effective in patients with stage 2 and 3 CKD (eGFR ≥30 mL/min/1.73m²) 6
  • Benefits persist even in patients with reduced renal function, though glucose-lowering efficacy decreases with declining eGFR 7

Patient Selection and Dosing

• Recommended for:

  • First-line therapy in patients with type 2 diabetes and established cardiovascular disease
  • Patients with heart failure (regardless of ejection fraction or diabetes status) 4
  • Patients with diabetic kidney disease 1

• Dosing:

  • Starting dose: 10 mg once daily
  • Can be increased to 25 mg once daily if needed
  • No dose adjustment required for mild to moderate hepatic impairment 2

• Renal dosing considerations:

  • Can be used with eGFR ≥30 mL/min/1.73m²
  • Not recommended for glycemic control when eGFR <45 mL/min/1.73m²
  • Contraindicated in patients with eGFR <30 mL/min/1.73m² 1, 2

Monitoring and Safety

• Monitor renal function:

  • Before initiation
  • Within 2-4 weeks after starting therapy
  • Periodically thereafter 4

• Common adverse effects:

  • Genital mycotic infections (most common)
  • Urinary tract infections
  • Volume depletion (more common in elderly or those on diuretics) 2

• Safety considerations:

  • Unlike canagliflozin, empagliflozin has not been associated with increased risk of amputation or bone fractures 3
  • No increased risk of stroke was observed (HR 1.08,95% CI 0.81-1.45) 8
  • Discontinue at least 3 days before scheduled surgery to prevent ketoacidosis 1

Clinical Pearls and Pitfalls

• Key pitfalls to avoid:

  • Delaying initiation in eligible patients (reduces likelihood of ever receiving this life-saving therapy) 4
  • Withholding due to mild renal impairment (beneficial with eGFR ≥30 mL/min/1.73m²) 4
  • Limiting use based on diabetes status (benefits extend beyond glycemic control) 4

• Important considerations:

  • If patient is on insulin or sulfonylureas, consider reducing doses by approximately 20% when initiating empagliflozin to prevent hypoglycemia 1
  • May contribute to intravascular volume contraction; consider reducing diuretic dose if applicable 1
  • Monitor for euglycemic diabetic ketoacidosis, especially during acute illness or surgical procedures 1

Empagliflozin represents a significant advancement in type 2 diabetes management, offering benefits that extend well beyond glycemic control to include substantial improvements in cardiovascular and renal outcomes, making it a cornerstone therapy for patients with type 2 diabetes, particularly those with established cardiovascular disease or at high cardiovascular risk.