What is the recommended treatment protocol for patients with type 2 diabetes using Synjardy (empagliflozin and metformin)?

Synjardy Treatment Protocol for Type 2 Diabetes

For patients with type 2 diabetes, Synjardy (empagliflozin/metformin combination) should be initiated when metformin monotherapy fails to achieve glycemic targets after approximately 3 months, with the combination providing superior HbA1c reduction of 1.9-2.1% from baseline while offering cardiovascular and renal protection. 1, 2

Initial Therapy vs Add-On Therapy

Starting Synjardy as Initial Therapy

• Begin with empagliflozin 10 mg/metformin 1000 mg twice daily in treatment-naïve patients with HbA1c between 7-10.5% 2
• This initial combination reduces HbA1c by approximately 2.0-2.1% from baseline, significantly superior to either component alone (p-value <0.01) 2
• The combination can be titrated to empagliflozin 25 mg/metformin 2000 mg daily based on glycemic response and tolerability 2

Adding Empagliflozin to Existing Metformin

• Add empagliflozin 10 mg once daily to patients inadequately controlled on metformin monotherapy (HbA1c ≥7%) 2, 1
• This provides an additional HbA1c reduction of 0.6-0.8% beyond metformin alone 2
• Titrate to empagliflozin 25 mg once daily if HbA1c target not achieved after 12 weeks 2

Dosing Considerations by Renal Function

eGFR ≥60 mL/min/1.73 m²

• Use standard dosing: metformin up to 2000 mg daily with empagliflozin 10-25 mg once daily 1
• Monitor kidney function at least annually 1

eGFR 45-59 mL/min/1.73 m²

• Continue metformin at same dose or reduce to half the maximum dose based on clinical factors 1
• Continue empagliflozin at standard dose (10-25 mg daily) 1
• Monitor kidney function every 3-6 months 1

eGFR 30-44 mL/min/1.73 m²

• Reduce metformin to half the maximum recommended dose (initiate at 500 mg daily if starting new) 1
• Continue empagliflozin at standard dose 1
• Monitor kidney function every 3-6 months 1

eGFR <30 mL/min/1.73 m²

• Discontinue both metformin and empagliflozin 1, 2
• Empagliflozin is not expected to be effective at this level of renal function 2

Prioritization for High-Risk Patients

Established ASCVD or High CV Risk

• Empagliflozin (component of Synjardy) is specifically recommended in patients with established cardiovascular disease or very high/high CV risk to reduce cardiovascular events and mortality 1
• The empagliflozin component reduces cardiovascular death by 38% and heart failure hospitalization by 35% in these patients 1
• Use Synjardy independent of baseline HbA1c in these populations 1

Heart Failure

• SGLT2 inhibitors (empagliflozin) are specifically recommended to lower risk of heart failure hospitalization 1
• Metformin should be considered if eGFR >30 mL/min/1.73 m² but avoided in unstable or hospitalized heart failure 1

Chronic Kidney Disease

• Most patients with T2D, CKD, and eGFR ≥30 mL/min/1.73 m² benefit from both metformin and empagliflozin (Grade 1A recommendation) 1
• SGLT2 inhibitors reduce progression of diabetic kidney disease 1

Triple Therapy Protocol

Adding to Metformin + Sulfonylurea

• Add empagliflozin 10 mg once daily to patients inadequately controlled on metformin plus sulfonylurea 2, 3
• This provides HbA1c reduction of 0.6-0.8% beyond dual therapy 2, 3
• Critical caveat: Hypoglycemia risk increases significantly with this combination (24% with sulfonylurea vs 2% without) 4, 3
• Consider reducing sulfonylurea dose by 50% when adding empagliflozin to prevent hypoglycemia 3

Monitoring and Titration Schedule

Week 0 (Initiation)

• Baseline HbA1c, eGFR, body weight, blood pressure 2
• Educate on genital mycotic infections (more common in females: 4-18% vs males: 0-3%) and urinary tract infections 2, 3

Week 12-16

• Assess HbA1c, weight, blood pressure 2
• If HbA1c target not met, increase empagliflozin from 10 mg to 25 mg daily 2

Week 24

• Reassess HbA1c, eGFR, body weight, blood pressure 2
• If HbA1c target still not met, add GLP-1 receptor agonist as third agent 1

Ongoing

• Monitor eGFR frequency based on renal function (annually if ≥60, every 3-6 months if <60) 1
• Monitor vitamin B12 levels periodically on metformin 1

Expected Outcomes

Glycemic Control

• HbA1c reduction of 1.9-2.1% with combination therapy vs 1.2-1.8% with metformin alone 2
• 26-39% of patients achieve HbA1c <7% on combination therapy 2

Weight and Blood Pressure

• Weight reduction of 2.0-2.9% from baseline 2
• Systolic blood pressure reduction of 4.1-4.8 mmHg (placebo-corrected) 2

Cardiovascular Benefits

• Empagliflozin component reduces cardiovascular death, particularly in patients with established ASCVD 1

Common Pitfalls to Avoid

• Do not continue metformin if eGFR drops below 30 mL/min/1.73 m² - this increases lactic acidosis risk 1, 2
• Do not continue empagliflozin if eGFR <30 mL/min/1.73 m² - it becomes ineffective 2
• Reduce sulfonylurea dose by 50% when adding empagliflozin to prevent hypoglycemia 3
• Counsel female patients specifically about genital mycotic infection risk (4-18% incidence) 2, 3
• Ensure adequate hydration to prevent volume depletion, especially in elderly patients or those on diuretics 2