How should the dose of Jardiance (empagliflozin) be adjusted according to the patient's estimated glomerular filtration rate and comorbid conditions such as heart failure or hepatic impairment?

How to Adjust Jardiance (Empagliflozin)

Dose Selection by Clinical Indication

For cardiovascular or renal protection, use a fixed dose of 10 mg once daily—do not increase to 25 mg, as both doses produce identical reductions in cardiovascular death, heart failure hospitalization, and renal outcomes. 1

Cardiovascular and Renal Protection

• Start empagliflozin 10 mg once daily when eGFR ≥ 20 mL/min/1.73 m² for cardiovascular or renal protection, regardless of diabetes status 1
• No dose titration is required or recommended for cardiorenal indications; all major outcome trials used fixed 10 mg or 25 mg doses with identical cardiovascular and mortality benefits 1
• The EMPA-REG OUTCOME trial demonstrated that 10 mg and 25 mg produced no dose-response relationship for cardiovascular death (38% reduction with both doses), all-cause mortality (32% reduction), or heart failure hospitalization 1

Glycemic Control in Type 2 Diabetes

• Begin with 10 mg once daily; if HbA1c remains above target after 4–12 weeks and eGFR ≥ 45 mL/min/1.73 m², escalate to 25 mg once daily 1
• The higher dose provides additional glucose lowering but no additional cardiovascular or renal benefit 1

Renal Function-Based Dosing Algorithm

eGFR (mL/min/1.73 m²)	Initiation	Continuation	Rationale
≥ 45	Start 10 mg daily; may increase to 25 mg for glycemic control	Continue current dose	Full glucose-lowering efficacy [1]
30–44	Start 10 mg daily only for CV/renal protection	Continue 10 mg daily	Glucose-lowering reduced, but CV/renal benefits persist [1]
20–29	May start 10 mg daily for CV/renal protection	Continue 10 mg daily	Minimal glycemic benefit; cardiorenal protection remains [1]
< 20	Do not initiate	May continue 10 mg daily until dialysis	Initiation not recommended; continuation may confer CV benefit [1]

Key Renal Considerations

• Dose modifications are driven by glucose-lowering efficacy, not safety; cardiovascular benefits persist down to eGFR 30 mL/min/1.73 m² with the 10 mg dose 1
• An expected eGFR dip of 3–5 mL/min/1.73 m² within 1–2 weeks is hemodynamic, reversible, and protective—do not discontinue empagliflozin in response to this change 1
• Do not stop empagliflozin when eGFR falls below 45 mL/min/1.73 m²; cardiovascular and renal benefits persist despite loss of glycemic efficacy 1

Concomitant Medication Adjustments

Insulin and Sulfonylureas

• When adding empagliflozin to insulin or sulfonylurea therapy, reduce the dose by ≈ 20% if baseline HbA1c is < 8.5% to lower hypoglycemia risk 1
• Discontinue sulfonylureas entirely when HbA1c is already < 8.5%, as the combination adds hypoglycemia risk without cardiovascular benefit 1

Diuretics

• Consider reducing concurrent diuretic doses at initiation, especially in elderly patients or those on loop diuretics, to prevent volume depletion 1
• Assess and correct volume status before starting empagliflozin 1

ACE Inhibitors and ARBs

• Continue ACE inhibitors or ARBs unchanged when starting empagliflozin 1

Metformin

• For patients with eGFR 30–44 mL/min/1.73 m², limit metformin to ≤ 1,000 mg daily 2, 1
• Stop metformin if eGFR falls < 30 mL/min/1.73 m² 2, 1

Special Populations

Older Adults

• Empagliflozin may be used in older adults with caution regarding volume depletion, particularly those ≥ 75 years or on loop diuretics 2
• Lower doses (10 mg) are preferred to minimize adverse effects while maintaining cardiovascular and renal benefits 1
• Metformin may be used safely if eGFR ≥ 30 mL/min/1.73 m², with dose reduction to ≤ 1,000 mg daily if eGFR 30–45 mL/min/1.73 m² 2

Hepatic Impairment

• No dose adjustment is required in patients with hepatic impairment, including severe impairment (Child-Pugh C), as increases in empagliflozin exposure are less than twofold 3

Contraindications and Precautions

Absolute Contraindications

• Type 1 diabetes due to increased risk of diabetic ketoacidosis 1

Temporary Discontinuation Required

• Hold empagliflozin ≥ 3 days before major surgery or any procedure requiring prolonged fasting to avoid postoperative euglycemic ketoacidosis 1
• Temporarily discontinue during acute illnesses with reduced oral intake, fever, vomiting, or diarrhea to prevent volume depletion and ketoacidosis 1

Volume Depletion Risk

• Assess volume status before initiation; correct any depletion and consider reducing diuretic doses 1
• Elderly patients and those on loop diuretics are at higher risk 1

Monitoring Recommendations

Parameter	Timing	Rationale
eGFR	Baseline, then 1–2 weeks after initiation	Detect expected hemodynamic dip (~3–5 mL/min/1.73 m²) [1]
eGFR	Every 3–6 months if eGFR 30–59 mL/min/1.73 m²; annually if ≥ 60 mL/min/1.73 m²	Ongoing renal trajectory assessment [1]
Blood glucose	Intensively for first 2–4 weeks, especially with insulin/sulfonylureas	Prevent hypoglycemia and detect early ketoacidosis [1]
Volume status	At each follow-up visit	Mitigate dehydration and hypotension risk [1]

Safety Profile and Adverse Events

Common Adverse Events

• Genital mycotic infections occur in ~4% (10 mg) and ~6% (25 mg) versus 1% with placebo; good daily hygiene mitigates risk 1
• Urinary tract infections and volume depletion are more frequent with 25 mg, particularly in elderly patients with reduced renal function 1

Serious but Rare Events

• Euglycemic diabetic ketoacidosis is rare but serious; instruct patients to seek immediate care for unexplained malaise, nausea, vomiting, or abdominal pain even when blood glucose is normal 1
• Adverse events leading to discontinuation were numerically fewer with empagliflozin than placebo in the EMPA-REG OUTCOME trial 1

Administration and Patient Education

Timing

• Empagliflozin may be taken with or without food at any time of day; morning dosing is preferred to reduce nocturia 1

Sick-Day Rules

• Hold empagliflozin during acute illness; maintain at least a low-dose insulin regimen in insulin-requiring patients even when empagliflozin is held 1
• Advise adequate hydration, especially in hot weather or during exercise 1

Expected Effects

• Patients should be counseled that increased urination is an expected effect due to renal glucose excretion 1

Common Pitfalls to Avoid

• Do not discontinue empagliflozin solely because eGFR falls below 45 mL/min/1.73 m²; cardiovascular and renal benefits persist despite loss of glycemic efficacy 1
• Do not stop the drug in response to the expected early eGFR dip (3–5 mL/min/1.73 m²); this change is hemodynamic, reversible, and protective 1
• Do not increase the dose from 10 mg to 25 mg for cardiovascular or renal protection, as the higher dose offers no additional benefit and raises adverse-event risk 1
• Do not combine sulfonylureas with empagliflozin when HbA1c is already at target, because this increases hypoglycemia risk without added cardiovascular advantage 1