Synjardy and Fatty Liver Disease
Synjardy (empagliflozin/metformin) is safe and appropriate for adults with type 2 diabetes and mild-to-moderate non-alcoholic fatty liver disease when renal function is adequate (eGFR ≥30 mL/min/1.73 m²), and this combination actively improves liver steatosis beyond glucose control alone. 1
Safety Profile in NAFLD/MASLD
Both components of Synjardy are explicitly endorsed for use in patients with metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD):
Metformin can be used in adults with compensated cirrhosis and preserved renal function, according to the 2024 EASL-EASD-EASO guidelines, though it should not be used in decompensated cirrhosis due to lactic acidosis risk. 1
SGLT2 inhibitors (empagliflozin) can be used in adults with Child-Pugh class A and B cirrhosis, demonstrating safety even in more advanced liver disease than mild-to-moderate NAFLD. 1
For patients with only mild-to-moderate fatty liver disease (no cirrhosis), both medications carry no hepatic contraindications and are considered first-line therapy. 1
Therapeutic Benefits for Liver Disease
The empagliflozin component provides direct benefits for fatty liver disease beyond metformin alone:
Empagliflozin added to metformin significantly reduced liver steatosis grade, CAP scores (293.5 to 267.0), and ALT levels (68.5 to 45.0) after 6 months in a 2023 study of T2DM patients with NAFLD. 2
The combination therapy improved steatosis grades by both ultrasound and fibroscan modalities more effectively than metformin monotherapy in multiple 2024 trials. 3, 4
Weight reduction with empagliflozin (mean -5.78 kg vs +0.93 kg with comparators) contributes to liver fat reduction, as weight loss is a key mechanism for NAFLD improvement. 3
Renal Function Requirements
Metformin dosing must be adjusted based on eGFR:
Standard dosing is safe for eGFR ≥45 mL/min/1.73 m² without dose adjustment. 1, 5
Reduce metformin to maximum 1,000 mg/day for eGFR 30-44 mL/min/1.73 m², with monitoring every 3-6 months. 1, 5
Metformin is contraindicated when eGFR <30 mL/min/1.73 m² due to lactic acidosis risk. 1
Empagliflozin can be initiated when eGFR ≥20 mL/min/1.73 m² for cardiorenal benefits, though glucose-lowering effects diminish below 45 mL/min/1.73 m². 1, 6
Clinical Implementation Algorithm
For a patient with T2DM, mild-to-moderate NAFLD, and adequate renal function:
Verify eGFR ≥30 mL/min/1.73 m² before prescribing Synjardy. 1
Start with standard dosing (empagliflozin 5-10 mg/metformin 500-1000 mg twice daily) if eGFR ≥45 mL/min/1.73 m². 7
If eGFR is 30-44 mL/min/1.73 m², limit total metformin to 1,000 mg/day maximum and consider using empagliflozin 10 mg once daily with metformin 500 mg twice daily. 1, 5
Monitor eGFR every 3-6 months once eGFR falls below 60 mL/min/1.73 m². 1, 5
Temporarily discontinue metformin during acute illness, contrast procedures, or hospitalization. 5
Important Caveats
Volume depletion monitoring is essential as empagliflozin has diuretic effects, particularly in patients on other diuretics or antihypertensives. 6
The combination provides cardiovascular and renal benefits independent of glucose lowering, making it appropriate even if HbA1c targets are already achieved. 1, 6
Liver enzyme monitoring is not required specifically for medication safety, though ALT/AST trends can help assess therapeutic response to treatment. 2, 3, 4
The presence of NAFLD is not a contraindication but rather an additional indication for this combination, as both components are safe in liver disease and empagliflozin actively improves hepatic steatosis. 1, 2, 4