Are SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors, such as canagliflozin (Canagliflozin), dapagliflozin (Dapagliflozin), or empagliflozin (Empagliflozin), used to treat type 1 diabetes mellitus (Type 1 DM)?

SGLT2 Inhibitors for Type 1 Diabetes Mellitus

SGLT2 inhibitors are not FDA-approved for use in type 1 diabetes mellitus due to significant risk of euglycemic diabetic ketoacidosis, despite potential glycemic benefits. 1, 2

Current Regulatory Status and Recommendations

• SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) are FDA-approved for type 2 diabetes but not for type 1 diabetes in the United States 1
• In the EU, dapagliflozin was approved at a dosage of 5 mg/day as an adjunct to insulin in adults with type 1 diabetes with a BMI ≥27 kg/m², when insulin alone does not provide adequate glycemic control 3
• The American Diabetes Association Standards of Care clearly state that SGLT2 inhibitors are not recommended for use in patients with type 1 diabetes mellitus 1

Risks Associated with SGLT2 Inhibitor Use in Type 1 Diabetes

• The FDA issued a specific warning about the risk of euglycemic diabetic ketoacidosis (DKA) in patients with type 1 diabetes treated with SGLT2 inhibitors 1
• SGLT2 inhibitor-associated DKA occurs in approximately 4% of people with type 1 diabetes, with risk 5-17 times higher than in people with T1D not treated with these agents 1
• Euglycemic DKA is particularly concerning as it can occur with normal or only slightly elevated blood glucose levels (<250 mg/dL), making it harder to detect 1, 2
• One analysis estimated that one additional case of ketoacidosis will occur for every 26 patient-years of exposure to SGLT2 inhibitors in type 1 diabetes 4

Risk Factors for DKA in Patients with Type 1 Diabetes on SGLT2 Inhibitors

• Very low-carbohydrate diets, prolonged fasting, and dehydration 1
• Excessive alcohol intake 1, 5
• Acute illness, infection, or surgical procedures 5
• Reduced insulin dosing or missed insulin doses 2
• Volume depletion 5

Potential Benefits of SGLT2 Inhibitors in Type 1 Diabetes

• Modest improvements in glycemic control when used as adjunct to insulin 3, 6
• Reduction in total daily insulin dose requirements 3, 7
• Weight loss benefits 3, 6
• No increased risk of hypoglycemia compared to insulin alone 3, 7
• Potential cardiovascular and renal benefits (though these are better established in type 2 diabetes) 6

Clinical Implications and Recommendations

• Patients with type 1 diabetes should be informed that SGLT2 inhibitors are not FDA-approved for type 1 diabetes 2
• The risk of DKA significantly outweighs the modest glycemic benefits in most patients with type 1 diabetes 4
• If considering off-label use (not recommended), patients should be carefully selected based on:
  • High BMI (≥27 kg/m²) 3
  • Adherence to insulin therapy 7
  • Ability to monitor ketones and recognize DKA symptoms 7
  • Close follow-up capability 7
• Patients who have previously experienced DKA should not be treated with SGLT2 inhibitors 1

Warning Signs and Monitoring

• Patients should be educated about symptoms of DKA including nausea, vomiting, abdominal pain, tiredness, and trouble breathing 2
• Ketone monitoring is essential, as DKA can occur even with blood glucose levels <200 mg/dL 1
• Patients should be instructed to stop taking SGLT2 inhibitors immediately and seek medical attention if symptoms of ketoacidosis develop 2

Conclusion

The use of SGLT2 inhibitors in type 1 diabetes carries significant risks, particularly euglycemic DKA, which outweigh the modest benefits in glycemic control for most patients. Current guidelines and FDA labeling do not support their use in type 1 diabetes in the United States.