What is the recommended dosing for Synjardy (empagliflozin and metformin hydrochloride)?

Synjardy Dosing

Synjardy (empagliflozin/metformin) should be initiated at empagliflozin 5 mg/metformin 500 mg twice daily with meals, then titrated based on glycemic control, renal function, and tolerability to a maximum of empagliflozin 12.5 mg/metformin 1000 mg twice daily. 1, 2

Initial Dosing Strategy

For treatment-naïve patients:

• Start with empagliflozin 5 mg/metformin 500 mg twice daily with meals 1, 2
• This lower starting dose minimizes gastrointestinal side effects from metformin, which are dose-dependent and often transient 3

For patients already on metformin monotherapy:

• Switch to empagliflozin 5 mg combined with their current metformin dose (up to 1000 mg twice daily) 1, 2
• Do not exceed empagliflozin 12.5 mg twice daily when using the combination formulation 1

Dose Titration Algorithm

Titration schedule:

• Increase metformin component by 500 mg increments weekly or every 2 weeks based on glycemic response and GI tolerability 2
• Target metformin dose is 1000 mg twice daily (2000 mg total daily), as doses above 2000 mg provide minimal additional efficacy with worse tolerability 3
• Maximum dose: empagliflozin 12.5 mg/metformin 1000 mg twice daily 1, 2

Expected HbA1c reduction:

• Initial combination therapy reduces HbA1c by approximately 1.9-2.1% from baseline (mean baseline 8.6-8.9%) over 24 weeks 4
• This is significantly superior to either component alone 4

Renal Function-Based Dosing Adjustments

Critical eGFR thresholds:

eGFR ≥60 mL/min/1.73 m²:

• No dose adjustment required for either component 3, 1
• Continue standard dosing and monitor renal function annually 3

eGFR 45-59 mL/min/1.73 m²:

• Continue empagliflozin at current dose (glucose-lowering efficacy maintained) 1
• Consider reducing metformin dose in certain high-risk conditions (elderly, volume depletion, concurrent diuretics) 3
• Monitor renal function every 3-6 months 3

eGFR 30-44 mL/min/1.73 m²:

• Do not initiate Synjardy in this population 1, 2
• If already on therapy, reduce metformin to half the dose (maximum 1000 mg daily) 3
• Discontinue empagliflozin if eGFR falls persistently below 45 mL/min/1.73 m² 1
• Monitor renal function every 3-6 months 3

eGFR <30 mL/min/1.73 m²:

• Contraindicated - discontinue both components immediately 1, 2

Administration Guidelines

Timing and food:

• Administer twice daily with meals to reduce metformin GI side effects 2
• Morning and evening dosing provides optimal 24-hour glucose control 1, 2

Perioperative management:

• Withhold Synjardy at least 3 days before major surgery or procedures requiring prolonged fasting to prevent euglycemic diabetic ketoacidosis 5
• Discontinue before iodinated contrast procedures in patients with eGFR 30-60 mL/min/1.73 m² 2
• Re-evaluate eGFR 48 hours after contrast; restart only if renal function is stable 2

Sick Day Rules

Temporarily discontinue Synjardy during:

• Acute illness with reduced oral intake, fever, vomiting, or diarrhea 6
• Severe dehydration or volume depletion 3, 1
• Any condition predisposing to lactic acidosis (metformin component) 3

Resume therapy only after:

• Patient has recovered from acute illness 6
• Normal oral intake is re-established 6
• Volume status is corrected 6

Hypoglycemia Risk Management

When combining with insulin or sulfonylureas:

• Reduce insulin secretagogue or insulin dose by 20-30% when initiating Synjardy to minimize hypoglycemia risk 1
• The combination itself has low intrinsic hypoglycemia risk when used without these agents 4, 7

Monitoring Requirements

Baseline assessment:

• eGFR and serum creatinine before initiation 1, 2
• Volume status assessment, especially in elderly or those on diuretics 1

Ongoing monitoring:

• Recheck eGFR within 1-2 weeks after initiation 6
• Monitor renal function at least annually if eGFR ≥60 mL/min/1.73 m², or every 3-6 months if eGFR 45-59 mL/min/1.73 m² 3
• Monitor vitamin B12 levels if on metformin >4 years, particularly in patients with anemia or neuropathy 3

Common Adverse Effects and Management

Gastrointestinal symptoms (metformin component):

• Occur in majority of patients initially but often improve over time 3
• Start with lower doses and titrate slowly to minimize symptoms 3
• Consider dose reduction if symptoms persist 3

Genital mycotic infections (empagliflozin component):

• Occur in approximately 6% of patients (particularly women) versus 1% on placebo 5, 8
• Educate patients on daily hygienic measures to reduce risk 6
• Treat promptly if infections occur 1

Volume depletion:

• Higher risk in elderly, those on diuretics, or with low baseline blood pressure 1
• Assess and correct volume status before initiating therapy 1
• Consider reducing concurrent diuretic doses 6

Special Populations

Pediatric patients (ages 10-17 with type 2 diabetes):

• Empagliflozin can be initiated at 10 mg daily (not as combination product) 5
• Metformin starting dose is 500 mg twice daily, titrated to maximum 2000 mg daily 3, 2

Elderly patients:

• Higher incidence of volume depletion and renal impairment 1
• Start with lower doses and monitor closely 1
• More frequent renal function monitoring required 3

Key Clinical Pitfalls to Avoid

• Do not continue metformin if eGFR falls below 30 mL/min/1.73 m² - this is an absolute contraindication due to lactic acidosis risk 2
• Do not initiate empagliflozin if eGFR <45 mL/min/1.73 m² - glucose-lowering efficacy is significantly reduced 1
• Do not forget to hold therapy during acute illness - both components carry risks during volume depletion 3, 6, 1
• Do not overlook vitamin B12 monitoring - metformin can cause deficiency, particularly with long-term use 3