Can SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors be used in patients with diabetes and elevated liver enzymes?

SGLT2 Inhibitors in Patients with Diabetes and Elevated Liver Enzymes

SGLT2 inhibitors can be safely used in patients with diabetes and elevated liver enzymes, and may actually provide benefits for liver health by reducing liver fat content and improving liver enzyme levels. 1, 2

Safety and Benefits for Liver Function

• SGLT2 inhibitors have demonstrated significant reductions in alanine aminotransferase (ALT) levels and liver fat content in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes 1, 2
• Multiple studies have shown that SGLT2 inhibitors can decrease hepatic fat content as measured by magnetic resonance imaging proton density fat fraction 2
• SGLT2 inhibitors have been shown to improve liver fibrosis indices in patients with fatty liver disease 1
• Recent evidence indicates SGLT2 inhibitors provide greater improvement in fatty liver index compared to DPP4 inhibitors in patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and diabetes 3

Mechanism of Action and Considerations

• SGLT2 inhibitors work independently of insulin by blocking glucose reabsorption in the proximal renal tubules, making them suitable for various stages of diabetes regardless of beta-cell function 4
• These medications can be used without regard to diabetes duration, provided renal function is acceptable 4
• SGLT2 inhibitors have demonstrated beneficial effects beyond glucose control, including weight reduction, blood pressure lowering, and improvements in metabolic parameters that may contribute to liver health 4

Dosing and Monitoring Considerations

• SGLT2 inhibitors should be used with caution in patients with renal insufficiency (GFR < 45 mL/min/1.73 m²) 4
• The 2022 KDIGO guidelines recommend SGLT2 inhibitors in all patients with eGFR above 20 mL/min/1.73 m² independent of the presence of albuminuria 4
• When initiating SGLT2 inhibitors, monitor for potential adverse effects including:
  • Genital mycotic infections (most common adverse event) 5
  • Volume depletion, especially if used with diuretics 4
  • Risk of euglycemic diabetic ketoacidosis (minimal when prescribed appropriately) 5

Special Considerations for Liver Disease

• SGLT2 inhibitors have shown promise in patients with metabolic liver disease, with robust data from patients with NAFLD/MAFLD 6
• These medications may have beneficial effects in patients with liver cirrhosis by affecting pathophysiological features shared with heart failure 6
• Approximately 17% of patients taking SGLT2 inhibitors may develop adverse events, with genitourinary tract infections being the most common 1

Cardiovascular and Renal Benefits

• Beyond their effects on liver enzymes, SGLT2 inhibitors provide significant cardiovascular and renal benefits 4
• The 2022 ADA standards of care specify that SGLT2 inhibitors or GLP-1 RAs can be used as first-line therapy with or without metformin in individuals with or at high risk for ASCVD, heart failure, or kidney disease 4
• SGLT2 inhibitors are recommended for patients with type 2 diabetes who have heart failure (with either reduced or preserved ejection fraction) to prevent heart failure hospitalizations 4

Practical Recommendations

• For patients with diabetes and elevated liver enzymes, SGLT2 inhibitors can be added to existing antihyperglycemic regimens when glycemic targets are not met 4
• When adding SGLT2 inhibitors to regimens that include insulin or sulfonylureas, consider reducing doses of these medications to prevent hypoglycemia 4
• Educate patients about potential adverse effects including modest volume contraction, blood pressure reduction, and weight loss 4
• Monitor liver enzymes periodically to assess improvement in hepatic function 1, 2

SGLT2 inhibitors represent a valuable therapeutic option for patients with diabetes and elevated liver enzymes, offering benefits for glycemic control while potentially improving liver health parameters.