What are the considerations for using SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors, such as empagliflozin (Empagliflozin) or canagliflozin (Canagliflozin), in patients with heart failure and type 1 diabetes mellitus (T1DM)?

SGLT2 Inhibitors in Heart Failure and Type 1 Diabetes Mellitus

SGLT2 inhibitors are not recommended for use in patients with type 1 diabetes mellitus (T1DM), even when these patients have heart failure, due to the significantly increased risk of euglycemic diabetic ketoacidosis. 1, 2, 3, 2

Regulatory Status and Contraindications

• SGLT2 inhibitors (empagliflozin, canagliflozin) are FDA-approved for type 2 diabetes mellitus but explicitly not recommended for type 1 diabetes mellitus 2, 3, 2
• FDA labels for these medications specifically list "not for the treatment of type 1 diabetes mellitus" as a limitation of use 3, 2
• The risk of euglycemic diabetic ketoacidosis is 5-17 times higher in patients with T1DM treated with SGLT2 inhibitors compared to those not on these agents 1
• SGLT2 inhibitor-associated DKA occurs in approximately 4% of people with type 1 diabetes 1

Benefits in Heart Failure

• SGLT2 inhibitors have demonstrated significant cardiovascular benefits in patients with heart failure with reduced ejection fraction (HFrEF), including: 4, 5
  • 25% reduction in the composite of cardiovascular death or HF hospitalization 4
  • 30% reduction in heart failure hospitalization 4
  • Benefits observed regardless of diabetes status in clinical trials 4, 6
• Multiple guidelines recommend SGLT2 inhibitors for heart failure management in patients with type 2 diabetes 4
• The 2022 AHA/ACC/HFSA guideline for heart failure management recommends SGLT2 inhibitors for patients with HFrEF to reduce hospitalization and mortality 4

Risks of SGLT2 Inhibitors in T1DM with Heart Failure

• Euglycemic diabetic ketoacidosis is the most serious risk, which can occur with normal or only slightly elevated blood glucose levels, making it harder to detect 1, 7
• Risk factors for DKA in T1DM patients on SGLT2 inhibitors include: 1
  • Very low-carbohydrate diets
  • Prolonged fasting or reduced food intake
  • Dehydration
  • Excessive alcohol intake
  • Volume depletion
• Recent case reports have documented euglycemic ketoacidosis even in non-diabetic patients with heart failure taking SGLT2 inhibitors 8, 7, suggesting the risk would be even higher in T1DM patients

Alternative Approaches for T1DM Patients with Heart Failure

• For T1DM patients with heart failure, standard heart failure therapies should be prioritized: 4
  • ACE inhibitors/ARBs/ARNI
  • Beta-blockers
  • Mineralocorticoid receptor antagonists
  • Diuretics as needed for volume management
• Metformin may be considered in patients with heart failure if eGFR >30 mL/min/1.73 m² 4
• GLP-1 receptor agonists have a neutral effect on heart failure risk and may be considered 4

Special Considerations

• If a clinician were to consider SGLT2 inhibitors in a T1DM patient with heart failure (which is not recommended), the following would be essential: 1, 9
  • Extensive patient education about DKA risk
  • Regular ketone monitoring regardless of blood glucose levels
  • Immediate discontinuation if ketoacidosis is suspected
  • Temporary discontinuation during periods of illness, fasting, or surgical procedures 9
  • Maintaining at least low-dose insulin to prevent ketoacidosis risk 9

Conclusion

• The risk-benefit ratio strongly favors avoiding SGLT2 inhibitors in T1DM patients, even those with heart failure 1, 2, 3, 2
• The significant risk of euglycemic DKA (which can be life-threatening) outweighs the potential cardiovascular benefits in this specific population 1, 8, 7
• Focus should remain on optimizing standard heart failure therapies and insulin management in T1DM patients with heart failure 4