Can Jardiance (Empagliflozin) be added to Metformin ER (Metformin Extended Release) from the beginning in patients with type 2 diabetes?

Initial Combination Therapy with Jardiance (Empagliflozin) and Metformin ER

Yes, Jardiance (empagliflozin) can be added to Metformin ER from the beginning of treatment for type 2 diabetes, especially in patients with high baseline HbA1c levels or those with established cardiovascular disease.

Evidence Supporting Initial Combination Therapy

The FDA label for Jardiance specifically supports its use as initial combination therapy with metformin:

• A clinical trial evaluated the efficacy and safety of empagliflozin in combination with metformin as initial therapy compared to the individual components alone 1
• At Week 24, initial therapy of Jardiance in combination with metformin provided statistically significant reductions in HbA1c compared to either medication alone 1

Benefits of Initial Combination Therapy

Initial combination therapy offers several advantages:

• More rapid attainment of glycemic goals - Particularly beneficial for patients with HbA1c levels more than 1.5% above target 2
• Complementary mechanisms of action - Empagliflozin works through an insulin-independent mechanism while metformin improves insulin sensitivity
• Cardiovascular benefits - Empagliflozin has demonstrated cardiovascular risk reduction, which may benefit patients with or at risk for cardiovascular disease 3
• Weight reduction - The combination provides greater weight loss than metformin alone, with empagliflozin contributing to a 2-3% reduction in body weight 1
• Blood pressure reduction - Empagliflozin significantly reduces systolic blood pressure by 4-5 mmHg when combined with metformin 1

When to Consider Initial Combination Therapy

Initial combination therapy should be considered in:

1. Patients with baseline HbA1c ≥9% (75 mmol/mol) 2, 3
2. Patients with established cardiovascular disease or at high risk 2, 3
3. Patients who need more rapid attainment of glycemic goals 2
4. Patients with multiple cardiovascular risk factors 3

Dosing Considerations

When initiating combination therapy:

• Start with Metformin ER 500 mg daily and gradually increase by 500 mg every 1-2 weeks to minimize gastrointestinal side effects 3
• Target dose of Metformin ER is typically 2000 mg daily 3
• Jardiance can be initiated at 10 mg once daily and increased to 25 mg if needed 1
• Fixed-dose combinations may improve medication adherence 2

Monitoring and Follow-up

• Evaluate glycemic response within 3 months of initiating therapy 2
• Monitor renal function regularly, as both medications require dose adjustment or discontinuation with declining renal function 3
• Check for side effects specific to each medication:
  • Metformin: GI intolerance, vitamin B12 deficiency
  • Empagliflozin: Genital mycotic infections, urinary tract infections, volume depletion

Common Pitfalls to Avoid

1. Therapeutic inertia - Failing to intensify therapy when HbA1c targets are not met within 3 months 3
2. Overlooking renal function - Both medications require monitoring of kidney function 3
3. Ignoring hydration status - Empagliflozin can cause volume depletion, especially in elderly patients or those on diuretics
4. Neglecting patient education - Patients should be informed about potential genital mycotic infections with SGLT2 inhibitors and the importance of adequate hydration

Conclusion

While traditional approaches have favored stepwise addition of medications, the evidence supports initial combination therapy with Jardiance and Metformin ER in selected patients, particularly those with higher baseline HbA1c levels or cardiovascular risk factors. This approach can lead to more rapid achievement of glycemic goals and potential cardiovascular benefits.