What is the recommended starting dose and titration of Synjardy (empagliflozin/metformin) for an adult with type 2 diabetes, non‑pregnant, with estimated glomerular filtration rate ≥45 mL/min/1.73 m²?

Synjardy Dosing in Adults

For adults with type 2 diabetes and eGFR ≥45 mL/min/1.73 m², start Synjardy at empagliflozin 10 mg/metformin 500 mg twice daily, then titrate metformin upward every 1–2 weeks based on glycemic response and tolerability, up to a maximum of empagliflozin 25 mg/metformin 1000 mg twice daily. 1

Initial Dose Selection

• If metformin-naïve: Begin with empagliflozin 10 mg/metformin 500 mg twice daily with meals to minimize gastrointestinal side effects. 1
• If already on metformin monotherapy: Switch to Synjardy containing empagliflozin 10 mg plus the patient's current metformin dose (up to 1000 mg per tablet, twice daily). 1
• If already on empagliflozin monotherapy: Add metformin starting at 500 mg twice daily, then titrate upward. 1

Titration Strategy

• Increase the metformin component by 500 mg increments every 1–2 weeks as tolerated to achieve glycemic targets. 1
• The maximum approved dose is empagliflozin 25 mg/metformin 1000 mg twice daily (total daily: empagliflozin 50 mg, metformin 2000 mg). 1
• Empagliflozin does not require titration; use either 10 mg or 25 mg once or twice daily depending on the fixed-dose combination chosen. 1

Renal Function Considerations

• eGFR ≥60 mL/min/1.73 m²: No metformin dose adjustment required; use standard dosing. 1
• eGFR 45–59 mL/min/1.73 m²: Continue current metformin dose without increase; consider dose reduction in elderly patients or those with liver disease. 1
• eGFR 30–44 mL/min/1.73 m²: Reduce metformin to a maximum of 1000 mg daily (500 mg twice daily). 1
• eGFR <30 mL/min/1.73 m²: Metformin is contraindicated; discontinue immediately. 1
• Empagliflozin can be initiated if eGFR ≥25 mL/min/1.73 m² for cardiovascular and renal protection, even when metformin must be stopped. 2, 3

Cardiovascular and Renal Protection

• Empagliflozin 10 mg or 25 mg daily provides robust cardiovascular and renal benefits independent of glycemic control, reducing kidney disease progression by 44% and cardiovascular death or heart failure hospitalization by 29%. 2
• For patients with eGFR 25–44 mL/min/1.73 m², empagliflozin should be continued at 10 mg or 25 mg daily for cardiorenal protection, even though glucose-lowering efficacy is minimal. 2, 3
• Empagliflozin reduces the risk of incident or worsening nephropathy by 39%, doubling of serum creatinine by 44%, and need for renal-replacement therapy by 55%. 4

Safety Precautions and Monitoring

• Assess volume status before initiation and correct any depletion; consider reducing concurrent diuretic doses to prevent excessive volume loss. 2
• Withhold empagliflozin at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis. 2
• Temporarily discontinue empagliflozin during acute illness with reduced oral intake, fever, vomiting, or diarrhea to prevent euglycemic diabetic ketoacidosis and volume depletion. 2
• Monitor renal function every 3–6 months if eGFR is 45–59 mL/min/1.73 m², or annually if eGFR ≥60 mL/min/1.73 m². 1
• An acute, reversible eGFR decline of 2–5 mL/min/1.73 m² within the first 2–4 weeks is expected and should not prompt discontinuation. 2
• Counsel patients about genital mycotic infections (occurring in ~6% of empagliflozin users vs. 1% with placebo) and emphasize daily hygiene. 2
• Educate patients on euglycemic diabetic ketoacidosis symptoms (malaise, nausea, vomiting, abdominal pain) even when blood glucose is normal. 2
• Monitor vitamin B12 levels if metformin is continued for more than 4 years. 1

Common Pitfalls to Avoid

• Do not discontinue empagliflozin when eGFR falls below 45 mL/min/1.73 m²; cardiovascular and renal benefits persist even when glycemic efficacy wanes. 2, 3
• Do not stop empagliflozin because of the expected initial eGFR dip in the first 2–4 weeks. 2
• Do not reduce empagliflozin dose below 10 mg for cardiovascular or renal indications, even at lower eGFR levels. 2
• Do not withhold ACE inhibitors or ARBs when starting empagliflozin; continue these agents unchanged. 2

Integration with Other Diabetes Medications

• When adding empagliflozin to insulin or sulfonylurea therapy, reduce doses of those agents to mitigate hypoglycemia risk and monitor glucose closely for 2–4 weeks. 2
• Empagliflozin is increasingly used in combination with metformin, GLP-1 receptor agonists, and/or insulin in routine practice. 5
• The combination of metformin and empagliflozin has low hypoglycemia risk; no preemptive dose reduction is needed. 2