Can Metformin and Jardiance Be Taken Together?
Yes, metformin and Jardiance (empagliflozin) can and should be taken together for type 2 diabetes management—this combination is explicitly recommended by major diabetes guidelines and has FDA approval as a fixed-dose combination therapy. 1, 2
Mechanism and Rationale
The combination works through complementary mechanisms that provide additive glycemic control:
- Metformin decreases hepatic glucose production and improves insulin sensitivity 1
- Empagliflozin reduces plasma glucose by enhancing urinary glucose excretion through SGLT2 inhibition 1
Each medication added to metformin typically provides an additional 0.7-1.0% reduction in HbA1c, making this combination highly effective for patients inadequately controlled on metformin alone. 1
Clinical Evidence Supporting Combination Use
The FDA has specifically studied and approved empagliflozin in combination with metformin, with clinical trials demonstrating:
- Statistically significant HbA1c reductions of 0.6-0.8% compared to metformin alone at 24 weeks 2
- Additional benefits including weight loss (approximately 2-4 kg) and systolic blood pressure reduction (4-5 mmHg) 1, 2
- Low hypoglycemia risk when used together without insulin or sulfonylureas 1
Fixed-dose combination tablets of empagliflozin/metformin are FDA-approved, which reduces pill burden and improves adherence. 3
Cardiovascular and Renal Benefits
For patients with established cardiovascular disease, heart failure, or chronic kidney disease, this combination is particularly beneficial:
- Empagliflozin has demonstrated cardiovascular mortality reduction and decreased heart failure hospitalizations in high-risk patients 1, 4
- The American College of Cardiology and American Diabetes Association specifically recommend SGLT2 inhibitors like empagliflozin for these populations, independent of A1C levels 1
- These benefits appear related to empagliflozin's diuretic effect and heart failure prevention rather than purely glycemic control 4
Safety Profile and Monitoring
The combination has a favorable safety profile with minimal hypoglycemia risk, but requires monitoring for specific adverse effects:
Metformin-Related Concerns:
- Gastrointestinal effects (bloating, diarrhea, abdominal discomfort) 1
- Vitamin B12 deficiency with long-term use—periodic testing recommended 1
- Contraindicated when eGFR <30 mL/min/1.73m² 5
Empagliflozin-Related Concerns:
- Genital mycotic infections (most common adverse effect) 1
- Rare risk of euglycemic diabetic ketoacidosis 1, 6
- Volume depletion and hypotension, especially with concurrent diuretics 4
- Should not be used when eGFR <45 mL/min/1.73m² 1
Metabolic Acidosis Risk:
While both drugs individually carry rare risks of metabolic acidosis (lactic acidosis with metformin, ketoacidosis with empagliflozin), the combination may theoretically increase this risk and should be monitored, particularly in patients with renal impairment or during acute illness. 6
Practical Implementation
Start this combination when:
- Metformin monotherapy fails to achieve glycemic targets after 3 months 1
- Patient has cardiovascular disease, heart failure, or chronic kidney disease (add empagliflozin regardless of A1C) 1
- Initial HbA1c is 1.5-2.0% above target (consider starting both simultaneously) 1
Monitoring schedule:
- Assess treatment efficacy within 3 months of initiation 1
- Check HbA1c every 3-6 months 1
- Monitor renal function before starting empagliflozin and periodically thereafter 1
- Regular monitoring for medication-specific adverse effects 1
Key Clinical Pitfalls to Avoid
- Do not use empagliflozin if eGFR <45 mL/min/1.73m²—efficacy is significantly reduced and adverse effects increase 1, 4
- Educate patients about ketoacidosis warning signs (nausea, vomiting, abdominal pain, fatigue) even with normal glucose levels 1
- Dose adjustment may be needed if adding insulin or sulfonylureas later to avoid hypoglycemia 1
- Consider extended-release metformin if gastrointestinal intolerance occurs 1