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

Role of Empagliflozin in Managing Type 2 Diabetes Mellitus

Empagliflozin (Jardiance) is strongly recommended for patients with type 2 diabetes mellitus, particularly those with established cardiovascular disease, as it significantly reduces cardiovascular mortality by 38% and all-cause mortality by 32% while providing effective glycemic control. 1, 2

Indications and Benefits

Empagliflozin is indicated for:

• Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
• Reduction of cardiovascular death risk in adults with type 2 diabetes mellitus and established cardiovascular disease 2

Cardiovascular Benefits

• The EMPA-REG OUTCOME trial demonstrated that empagliflozin:
  • Reduced the composite outcome of MI, stroke, and cardiovascular death by 14% 1
  • Reduced cardiovascular death by 38% 1, 3
  • Reduced hospitalization for heart failure by 36% 3
  • Reduced all-cause mortality by 32% 3

Glycemic Control

• Provides HbA1c reductions of 0.7-1.0% 4
• Effective as monotherapy or as add-on to other glucose-lowering agents 3
• Low risk of hypoglycemia unless combined with insulin or insulin secretagogues 3

Additional Benefits

• Moderate weight reduction (2.1-2.5 kg) 3
• Blood pressure reduction (2.9-5.2 mmHg systolic) 3
• Renoprotective effects in patients with chronic kidney disease 5

Dosing and Administration

• Starting dose: 10 mg once daily in the morning, with or without food 2
• May increase to 25 mg daily in patients who tolerate the lower dose 2
• For patients with volume depletion, correct this condition before initiating empagliflozin 2

Renal Function Considerations

• Assess renal function before initiation and periodically thereafter 2
• Do not initiate in patients with eGFR <45 mL/min/1.73 m² 2
• Discontinue if eGFR persistently falls below 45 mL/min/1.73 m² 2

Patient Selection

Preferred Candidates

• Patients with established cardiovascular disease 1, 4
• Patients with heart failure 1, 4
• Patients requiring multiple agents for glycemic control 4
• Patients who would benefit from weight loss 4, 3

Cautions and Contraindications

• Contraindicated in patients with:
  • History of serious hypersensitivity to empagliflozin 2
  • Severe renal impairment, end-stage renal disease, or dialysis 2
• Use with caution in:
  • Elderly patients (increased risk of volume depletion) 2
  • Patients with low systolic blood pressure 2
  • Patients on diuretics 2

Monitoring and Safety Considerations

Common Adverse Effects

• Genital mycotic infections (counsel patients on personal hygiene) 4, 2, 3
• Risk of volume depletion and hypotension 2

Serious Adverse Effects

• Euglycemic diabetic ketoacidosis (rare but serious) 4, 2
  • Monitor for symptoms: nausea, vomiting, abdominal pain, dyspnea 4, 2
• Unlike canagliflozin, empagliflozin has not been associated with increased risk of lower limb amputations 1, 6

Monitoring Recommendations

• Assess renal function before initiation and periodically thereafter 2
• Monitor for signs and symptoms of hypotension, especially in at-risk patients 2
• Monitor for genital mycotic infections and urinary tract infections 4
• Monitor for euglycemic diabetic ketoacidosis 4, 2
• When used with insulin or sulfonylureas, monitor for hypoglycemia and consider dose reductions of these agents 4

Place in Therapy

First-Line Therapy

• Metformin remains first-line therapy for most patients with type 2 diabetes 4

Second-Line Therapy

• Empagliflozin is recommended as second-line therapy, particularly for patients with:
  • Established cardiovascular disease 1, 4
  • Heart failure 1, 4
  • Chronic kidney disease (if eGFR ≥45 mL/min/1.73 m²) 5

Combination Therapy

• Can be effectively combined with:
  • Metformin 4
  • DPP-4 inhibitors 4
  • GLP-1 receptor agonists 4
  • Insulin (may need to reduce insulin dose by approximately 20%) 4
  • Sulfonylureas (may need dose adjustment to prevent hypoglycemia) 4

By incorporating empagliflozin into the treatment regimen for appropriate patients with type 2 diabetes, clinicians can provide effective glycemic control while simultaneously reducing cardiovascular risk and offering additional benefits of weight loss and blood pressure reduction.