When to Start Jardiance (Empagliflozin)
Start empagliflozin immediately in adults with type 2 diabetes who have heart failure (any ejection fraction), chronic kidney disease (eGFR ≥20 mL/min/1.73 m² with albuminuria ≥200 mg/g), or established atherosclerotic cardiovascular disease—regardless of baseline A1C or current glucose control.
Primary Indications (Prioritized by Mortality/Morbidity Benefit)
1. Heart Failure (Strongest Indication)
- Start empagliflozin 10 mg daily in ANY adult with heart failure (reduced OR preserved ejection fraction), with or without diabetes 1, 2
- This is the most compelling indication based on mortality reduction
- eGFR threshold: ≥20 mL/min/1.73 m² (though trial data strongest for eGFR ≥30) 1
- Do not wait for optimization of other guideline-directed medical therapy—start early 1
2. Chronic Kidney Disease with Type 2 Diabetes
Initiate empagliflozin if:
- eGFR 20-60 mL/min/1.73 m² AND albuminuria (UACR ≥200 mg/g) 3, 4, 5
- This prevents CKD progression, cardiovascular events, and heart failure hospitalizations
- Can start with eGFR >30 mL/min/1.73 m² per FDA labeling, though benefit extends to eGFR ≥20 3, 2
Consider empagliflozin if:
- eGFR 20-45 mL/min/1.73 m² with UACR <200 mg/g 5
- Weaker evidence but reasonable given consistent class effects
3. Established Atherosclerotic Cardiovascular Disease with Type 2 Diabetes
- Start empagliflozin in patients with prior MI, stroke, or peripheral arterial disease to reduce cardiovascular death and heart failure hospitalization 6, 7, 8
- Most trial participants were already on metformin (74-77%) 6
- Baseline A1C in trials ranged 7.1-8.7% 6, 7
4. Glycemic Control in Type 2 Diabetes (Lowest Priority)
Start empagliflozin 10 mg daily if:
- eGFR ≥30 mL/min/1.73 m² 2
- Can increase to 25 mg for additional glucose lowering if tolerated 2
- Not recommended for glycemic control if eGFR <30 (ineffective due to mechanism) 2
Practical Algorithm
Step 1: Check for absolute contraindications
- Dialysis (contraindicated) 2
- Type 1 diabetes (not recommended—increased ketoacidosis risk) 1, 2
- History of hypersensitivity/angioedema to empagliflozin 2
Step 2: Assess eGFR
- eGFR ≥30: Can start for any indication 6, 3, 2
- eGFR 20-29: Start for heart failure or CKD with albuminuria; insufficient data for cardiovascular disease alone 3, 5, 2
- eGFR <20: Insufficient data; not recommended 1, 2
Step 3: Identify high-priority indication (start immediately if present)
- Heart failure → START (10 mg daily)
- CKD with UACR ≥200 mg/g → START (10 mg daily)
- Established ASCVD → START (10 mg daily)
- None of above but need glucose control → START if eGFR ≥30 (10 mg, can increase to 25 mg)
Step 4: Pre-initiation assessment
- Correct volume depletion before starting 2
- Consider reducing diuretic dose in high-risk patients 9
- Reduce insulin/sulfonylurea doses to prevent hypoglycemia 9
Dosing Specifics
- Standard dose: 10 mg once daily (morning, with or without food) 6, 2
- For additional glycemic control: Increase to 25 mg daily if tolerating 10 mg 2
- Continue therapy even if eGFR falls below initiation threshold unless not tolerated or dialysis initiated 3, 9, 5
Critical Safety Considerations
Ketoacidosis Risk (Most Serious)
- Withhold during prolonged fasting, surgery, or critical illness 9, 5, 2
- Maintain at least low-dose insulin in insulin-requiring patients 9, 2
- Educate patients on ketoacidosis symptoms (can occur with normal glucose) 2
Common Manageable Side Effects
- Genital mycotic infections (10-15% in women, lower in men): Counsel on hygiene; treat with antifungals without discontinuing 1, 9
- Volume depletion: Monitor in elderly, those on diuretics, or with low baseline blood pressure 9, 2
- Transient eGFR decline (3-5 mL/min/1.73 m² in first 4 weeks): Expected and not an indication to stop 9, 5
Medication Adjustments
- Reduce insulin/sulfonylurea doses when starting to prevent hypoglycemia 9
- Consider reducing diuretics in volume-depleted patients 9
- No intrinsic hypoglycemia risk with empagliflozin alone 6, 10, 11
Key Pitfalls to Avoid
Waiting for A1C >7% to start: The cardiovascular/renal benefits occur independent of glucose lowering—start based on comorbidities, not A1C 6, 3, 4
Stopping when eGFR falls below 30: Continue therapy unless dialysis initiated or not tolerated 3, 9, 5
Delaying in heart failure patients: Mortality benefit is substantial—start early, don't wait for GDMT optimization 1
Not counseling on sick day rules: Patients must know to stop during prolonged fasting/illness to prevent ketoacidosis 9, 5, 2
Assuming all SGLT2 inhibitors are equivalent: Empagliflozin specifically has FDA approval for heart failure and cardiovascular death reduction 2