Jardiance (Empagliflozin) and Erythrocytosis: Risks and Management
SGLT2 inhibitors like Jardiance (empagliflozin) are associated with a significant risk of erythrocytosis (16.9% prevalence), but this condition rarely leads to thrombotic events and should be monitored rather than necessitating discontinuation in most patients with diabetes. 1, 2
Prevalence and Risk Factors for SGLT2 Inhibitor-Induced Erythrocytosis
SGLT2 inhibitors commonly cause increases in hemoglobin and hematocrit levels:
- Prevalence of erythrocytosis: 16.9% of patients on SGLT2 inhibitors 2
- Median hemoglobin increase: 1.0 g/dL (IQR, 0.4-1.8) 2
- Hematocrit typically increases by approximately 1.50% 1
Major risk factors for developing erythrocytosis:
- Male sex (OR 3.24-4.12) 1, 2
- Current smoking (OR 2.00-2.41) 1, 2
- BMI ≥ 25 kg/m² (OR 1.97) 2
- Use of empagliflozin vs. dapagliflozin (OR 1.16) 1
- Combined use with testosterone replacement therapy (OR 3.80 compared to SGLT2i alone) 3
Thrombotic Risk Assessment
Despite theoretical concerns about hyperviscosity, recent evidence shows:
Erythrocytosis from SGLT2 inhibitors is not significantly associated with increased risk of:
Thrombotic events are rare (0.5% of patients) and primarily associated with:
- Pre-existing conditions requiring antiplatelet/anticoagulant therapy
- Baseline erythrocytosis (present before SGLT2i initiation) 2
Management Approach for Patients with Diabetes and Erythrocytosis
1. Monitoring Protocol
- Obtain baseline hemoglobin/hematocrit before initiating Jardiance
- Monitor hemoglobin/hematocrit at 3-6 months after initiation
- Continue periodic monitoring (every 6-12 months) in patients with risk factors
2. Risk Stratification
- Low Risk: No baseline erythrocytosis, no cardiovascular disease, female, non-smoker
- Moderate Risk: Male sex, smoking, BMI ≥25 kg/m²
- High Risk: Combined use with testosterone, baseline erythrocytosis, multiple risk factors
3. Management Based on Risk Level
- Low Risk: Standard monitoring
- Moderate Risk: More frequent monitoring (every 3-6 months)
- High Risk: Consider alternative agents (GLP-1 RAs) if appropriate
4. When to Consider Discontinuation
- Severe erythrocytosis (hemoglobin >18 g/dL or hematocrit >54%)
- Symptoms of hyperviscosity (headache, blurred vision, fatigue)
- Development of thrombotic events with concurrent erythrocytosis
Benefits of Continuing Jardiance Despite Mild-Moderate Erythrocytosis
SGLT2 inhibitors provide significant cardiorenal benefits that often outweigh the risks of mild-moderate erythrocytosis:
- Reduced risk of cardiovascular death, MI, or stroke (HR 0.86) 4
- Reduced risk of hospitalization for heart failure (HR 0.61) 4
- Reduced risk of kidney disease progression (HR 0.56-0.61) 4
Special Considerations
Patients with Chronic Kidney Disease
- SGLT2 inhibitors are recommended for patients with CKD (eGFR 30-90 mL/min/1.73m²) 4
- Contraindicated in severe renal impairment (eGFR <30 mL/min/1.73m²) 4, 5
Patients on Concurrent Medications
- Testosterone therapy: Significantly increases risk of erythrocytosis (OR 3.80) 3
- Diuretics: Consider reducing doses when initiating SGLT2 inhibitors 5
Alternative Agents When Erythrocytosis is Concerning
- GLP-1 receptor agonists (liraglutide, semaglutide) provide cardiovascular benefits without increasing erythrocytosis risk 5
- DPP-4 inhibitors are weight-neutral with low hypoglycemia risk 5
Clinical Pearls
- Mild erythrocytosis from SGLT2 inhibitors appears to be a class effect and is generally benign
- The cardiovascular and renal benefits of SGLT2 inhibitors typically outweigh the theoretical risks of erythrocytosis
- Discontinuation of therapy typically leads to resolution of erythrocytosis 6
- Patients with pre-existing cardiovascular disease should be monitored more closely, but SGLT2 inhibitor-induced erythrocytosis alone is rarely a reason to discontinue therapy