What is the recommended use of Jardiance (empagliflozin) in patients with type 2 diabetes mellitus?

Recommended Use of Jardiance (Empagliflozin) in Type 2 Diabetes Mellitus

Empagliflozin (Jardiance) is recommended as a first-line add-on therapy to metformin for patients with type 2 diabetes mellitus, particularly in those with established cardiovascular disease, heart failure, or chronic kidney disease, regardless of A1C levels.

Indications and Dosing

• FDA-approved indications 1:

  • As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
  • To reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease

• Dosing:

  • Starting dose: 10 mg once daily, taken in the morning with or without food 1
  • May be increased to 25 mg once daily if needed for additional glycemic control 1
  • Do not initiate if eGFR is below 45 mL/min/1.73 m² 1
  • Discontinue if eGFR falls persistently below 45 mL/min/1.73 m² 1

Patient Selection Algorithm

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

2. When to add empagliflozin:

   • If A1C target not achieved after approximately 3 months on metformin 2
   • Priority populations (add regardless of A1C level):
     • Patients with established ASCVD or high ASCVD risk 2
     • Patients with heart failure (with reduced or preserved ejection fraction) 3
     • Patients with chronic kidney disease 2, 3

3. Contraindications:

   • Severe renal impairment (eGFR <45 mL/min/1.73 m²) 1
   • History of serious hypersensitivity to empagliflozin 1
   • Type 1 diabetes or diabetic ketoacidosis 1

Clinical Benefits

Glycemic Control

• Moderate glucose-lowering effect: reduces A1C by approximately 0.7-1.0% 2, 4
• Low intrinsic risk of hypoglycemia due to insulin-independent mechanism 4, 5

Cardiovascular Benefits

• Reduces cardiovascular death by 38% in patients with established cardiovascular disease 6
• Reduces risk of major adverse cardiovascular events (MACE) by 14% 6
• Reduces all-cause mortality by 32% 6
• Reduces hospitalization for heart failure across the spectrum of heart failure (HFrEF, HFmrEF, HFpEF) 2, 3

Other Benefits

• Modest weight reduction 4
• Blood pressure reduction 4
• Renoprotective effects: slows decline in renal function 3, 6

Monitoring and Safety Considerations

• Before initiation:

  • Assess renal function (eGFR) 1
  • Assess volume status, especially in elderly patients or those on diuretics 1

• After initiation:

  • Monitor renal function within 2-4 weeks 3
  • Monitor for signs of genital mycotic infections 1
  • Consider lowering dose of insulin or insulin secretagogues if used concomitantly to reduce hypoglycemia risk 1

• Common adverse effects:

  • Urinary tract infections 1
  • Genital mycotic infections (more common in women) 1
  • Volume depletion/hypotension (particularly in elderly patients) 1

• Rare but serious adverse effects:

  • Diabetic ketoacidosis (can occur with normal blood glucose levels) 1
  • Acute kidney injury 1
  • Urosepsis and pyelonephritis 1

Combination Therapy Considerations

• Preferred combinations:

  • With metformin as first-line combination 2
  • Can be combined with GLP-1 receptor agonists for complementary effects 2, 3
  • Can be added to insulin therapy (may allow for insulin dose reduction) 5

• Combinations requiring caution:

  • With diuretics (increased risk of volume depletion) 1
  • With nephrotoxic drugs (increased risk of renal adverse effects) 7

Special Populations

• Elderly patients: Higher incidence of adverse reactions related to volume depletion; monitor closely 1
• Patients with renal impairment: Benefits seen in patients with eGFR ≥20 mL/min/1.73 m², but FDA approval requires eGFR ≥45 mL/min/1.73 m² 3, 1
• Patients with heart failure: Beneficial across all ejection fraction ranges; consider early initiation 3

Key Practice Points

• Empagliflozin should be considered early in the treatment algorithm for patients with type 2 diabetes, especially those with cardiovascular disease or risk factors 2
• Benefits extend beyond glycemic control to include cardiovascular and renal protection 6
• Unlike some other SGLT2 inhibitors, empagliflozin has not been associated with increased risk of amputation or bone fractures 4
• Consider initiating before hospital discharge in patients with heart failure for improved adherence and outcomes 3