What is the recommended use and dosage of Empagliflozin (Jardiance) for patients with type 2 diabetes mellitus?

Empagliflozin (Jardiance) for Type 2 Diabetes Mellitus

Recommended Dosing

Initiate empagliflozin at 10 mg orally once daily, taken in the morning with or without food, which provides optimal cardiovascular and renal benefits without requiring dose titration. 1, 2, 3

• The 10 mg daily dose is sufficient for cardiovascular risk reduction and does not require titration for these benefits 1, 2
• If additional glycemic control is needed after adequate trial, the dose may be increased to 25 mg once daily, though this provides only incremental glucose-lowering without additional cardiovascular protection 1, 2, 3
• The 25 mg dose demonstrated superior HbA1c and fasting plasma glucose reduction in network meta-analysis, particularly with treatment duration ≥12 weeks 4

Primary Indications

Empagliflozin is recommended as adjunct to diet and exercise for three distinct purposes in adults with type 2 diabetes:

1. Cardiovascular Risk Reduction

• Empagliflozin is specifically recommended to reduce cardiovascular death in patients with type 2 diabetes and established cardiovascular disease 5, 3
• The EMPA-REG OUTCOME trial demonstrated 38% reduction in cardiovascular death (3.7% vs 5.9% placebo, HR 0.62, P<0.001) 5
• Empagliflozin reduced major adverse cardiovascular events by 14% and hospitalization for heart failure by 35% 5, 6
• Benefits are consistent across all KDIGO chronic kidney disease risk categories 6

2. Heart Failure Prevention

• SGLT2 inhibitors including empagliflozin are recommended to lower risk of heart failure hospitalization in patients with type 2 diabetes and cardiovascular disease or multiple risk factors 5
• Empagliflozin consistently reduced heart failure outcomes across the entire spectrum of heart failure risk, from low-risk patients to those with established heart failure 7

3. Chronic Kidney Disease Progression

• Empagliflozin is recommended to reduce chronic kidney disease progression and cardiovascular events in patients with eGFR ≥20 mL/min/1.73 m² 5
• The drug reduced incident or worsening nephropathy by 39% (12.7% vs 18.8% placebo, HR 0.61, P<0.001) 5, 8
• Empagliflozin reduced doubling of serum creatinine by 44% and need for renal replacement therapy by 55% 8

Renal Function Considerations

Critical dosing adjustments based on kidney function:

• eGFR ≥45 mL/min/1.73 m²: No dose adjustment required; initiate at 10 mg daily 1, 2, 3
• eGFR 30-44 mL/min/1.73 m²: May continue for cardiovascular/renal benefits but not recommended for glycemic control 1, 2
• eGFR 20-29 mL/min/1.73 m²: May be used for cardiovascular/renal benefits based on recent evidence, though FDA label states not to initiate below 45 mL/min/1.73 m² 5, 3
• eGFR <20 mL/min/1.73 m² or dialysis: Contraindicated 1, 2, 3
• Assess renal function before initiating and discontinue if eGFR falls persistently below 45 mL/min/1.73 m² 3

Concomitant Medication Adjustments

When initiating empagliflozin, reduce hypoglycemia risk by adjusting other diabetes medications:

• Reduce total daily insulin dose by approximately 20% 1, 2
• Consider reducing or stopping sulfonylureas or glinides 1, 2
• These adjustments are critical as empagliflozin carries low inherent hypoglycemia risk when used alone but increases risk when combined with insulin secretagogues 9

Perioperative Management

Discontinue empagliflozin at least 3 days before major surgery or procedures with prolonged fasting to prevent postoperative ketoacidosis 10, 1, 2

• Resume only when patient is clinically stable and has resumed oral intake 10
• This precaution is essential as SGLT2 inhibitors can precipitate euglycemic diabetic ketoacidosis in surgical settings 3

Safety Monitoring

Key adverse effects requiring monitoring:

• Genital mycotic infections: Most common adverse effect (≥5% incidence), more frequent in women 3, 6, 9
• Urinary tract infections: Common (≥5% incidence) 3
• Volume depletion/hypotension: Assess and correct volume status before initiating, especially in elderly, those with low systolic blood pressure, renal impairment, or on diuretics 3
• Diabetic ketoacidosis: Rare but serious; assess patients presenting with metabolic acidosis regardless of blood glucose level 3
• Acute kidney injury: Consider temporary discontinuation in settings of reduced oral intake or fluid losses 3
• Urosepsis and pyelonephritis: Evaluate and treat urinary tract infections promptly 3

Special Populations

• Elderly patients: Higher incidence of volume depletion and renal function-related adverse reactions; careful monitoring required 3
• Pregnancy: Advise females of potential fetal risk, especially during second and third trimesters 3
• Lactation: Not recommended when breastfeeding 3
• Pediatric use: May be used in children aged 10-17 years with type 2 diabetes at same 10 mg starting dose 2

Common Pitfalls to Avoid

• Do not initiate in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) per FDA label, though emerging evidence supports use down to eGFR 20 mL/min/1.73 m² for cardiovascular/renal benefits 5, 2, 3
• Do not fail to reduce insulin or sulfonylurea doses when starting empagliflozin, as this substantially increases hypoglycemia risk 1, 2
• Do not continue through surgical procedures without 3-day washout period, as this increases ketoacidosis risk 1, 2
• Do not use for treatment of type 1 diabetes or diabetic ketoacidosis 3