Synjardy Dose Titration from Once to Twice Daily
When increasing Synjardy (empagliflozin/metformin) from once daily to twice daily, the metformin component should be increased in 500 mg increments every 2 weeks until reaching the target dose of 1 g twice daily, based on tolerability. 1
Titration Schedule
The recommended approach follows standard metformin titration guidelines:
- Start with 500 mg once daily (if not already at this dose) 1
- Increase by 500 mg every 2 weeks until reaching the target dose 1
- Target dose: 1 g (1000 mg) twice daily 1
- Adjust based on gastrointestinal tolerability 1
Key Considerations for Dose Escalation
Renal Function Requirements
Before any dose adjustment, verify kidney function: 1
- eGFR ≥60 mL/min/1.73 m²: Continue same dose without adjustment 1
- eGFR 45-59 mL/min/1.73 m²: Consider dose reduction in certain conditions 1
- eGFR 30-44 mL/min/1.73 m²: Halve the metformin dose 1
- eGFR <30 mL/min/1.73 m²: Do not initiate or continue metformin 1
Empagliflozin Component
The empagliflozin component does not require gradual titration and can be given at full dose immediately, though its glucose-lowering efficacy is reduced with declining eGFR (cardiovascular and renal benefits remain preserved). 2
Modified Release Formulation Advantage
If available, use the extended-release (modified release) metformin preparation to minimize gastrointestinal side effects during titration. 1
Monitoring During Titration
- Monitor kidney function every 3-6 months when eGFR is <60 mL/min/1.73 m² 1
- Monitor for gastrointestinal symptoms (nausea, diarrhea) that may require slower titration 1
- Check vitamin B12 levels if metformin use exceeds 4 years 1
Common Pitfalls to Avoid
- Do not increase metformin faster than every 2 weeks, as this significantly increases gastrointestinal intolerance 1
- Do not ignore renal function assessment before dose escalation, as metformin accumulation in renal impairment increases lactic acidosis risk 1
- Discontinue empagliflozin at least 3 days before planned surgery to prevent postoperative ketoacidosis 2