What are the recommendations for using SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors, such as empagliflozin (Jardiance) or canagliflozin (Invokana), in patients with Heart Failure with reduced Ejection Fraction (HFrEF) and Type 1 Diabetes Mellitus (T1DM)?

SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction and Type 1 Diabetes Mellitus

SGLT2 inhibitors (dapagliflozin or empagliflozin) are strongly recommended for patients with HFrEF to reduce the risk of heart failure hospitalization and death, but they are not recommended for patients with Type 1 Diabetes Mellitus due to increased risk of diabetic ketoacidosis.

Recommendations for HFrEF Patients

Benefits in Heart Failure with Reduced Ejection Fraction

• SGLT2 inhibitors (specifically dapagliflozin and empagliflozin) are recommended as foundational therapy for patients with HFrEF to reduce the risk of heart failure hospitalization and death 1
• These medications should be used alongside other guideline-directed medical therapy including ACE inhibitors, mineralocorticoid receptor antagonists (MRAs), and beta-blockers 1
• The benefits of SGLT2 inhibitors in HFrEF are seen regardless of the presence or absence of diabetes 1
• Clinical trials have demonstrated a 21-35% reduction in hospitalization for heart failure with SGLT2 inhibitors 1, 2

Timing and Implementation

• SGLT2 inhibitors should be initiated early in the treatment course for HFrEF patients 2
• The clinical benefits of these medications appear rapidly, with meaningful reductions in clinical events within days to weeks of initiation 2
• These drugs can be initiated regardless of whether patients are already receiving other heart failure medications 2

Safety Profile in Heart Failure

• SGLT2 inhibitors are generally well-tolerated in HFrEF patients with minimal effects on blood pressure 2
• They provide renal protective effects and reduce the risk of hyperkalemia, which can help improve tolerance of other heart failure medications 2
• They do not increase the risk of acute kidney injury in properly selected patients 2

Cautions in Type 1 Diabetes Mellitus

Risk of Diabetic Ketoacidosis

• SGLT2 inhibitors are not recommended for patients with Type 1 Diabetes Mellitus due to increased risk of diabetic ketoacidosis 1
• None of the major guidelines recommend SGLT2 inhibitors for T1DM patients, even those with heart failure 1
• The risk of diabetic ketoacidosis is particularly concerning in T1DM patients as it can be life-threatening 1

Alternative Approaches for T1DM Patients with HFrEF

• For T1DM patients with HFrEF, standard heart failure therapies should be prioritized:
  • ACE inhibitors or ARBs 1
  • Beta-blockers 1
  • Mineralocorticoid receptor antagonists 1
  • Diuretics as needed for congestion 1
• Sacubitril/valsartan can be considered as a replacement for ACE inhibitors or ARBs in appropriate patients 1

Special Considerations

Monitoring and Follow-up

• Regular monitoring of renal function is recommended when initiating SGLT2 inhibitors 1
• Patients should be educated about the symptoms of diabetic ketoacidosis, especially those with diabetes 1
• Volume status should be assessed regularly as these medications have diuretic effects 1

Ejection Fraction Considerations

• The benefits of SGLT2 inhibitors extend to patients with mildly reduced ejection fraction (HFmrEF, LVEF 41-49%) 1
• In the EMPEROR-Preserved trial, empagliflozin showed benefit in patients with LVEF >40%, with a 21% reduction in the composite endpoint of cardiovascular death or heart failure hospitalization 1, 3

Conclusion for Clinical Practice

For patients with HFrEF without T1DM, SGLT2 inhibitors should be part of standard therapy. For the specific population with both HFrEF and T1DM, the risk of diabetic ketoacidosis outweighs the potential benefits, and alternative heart failure therapies should be optimized instead.