Can Farxiga (dapagliflozin) be used in type 1 diabetics?

Use of Farxiga (Dapagliflozin) in Type 1 Diabetes

Farxiga (dapagliflozin) should not be used in patients with type 1 diabetes in the United States due to increased risk of diabetic ketoacidosis (DKA), except in very specific circumstances with extreme caution and risk mitigation strategies. 1

Regulatory Status and Evidence

Dapagliflozin is explicitly contraindicated for blood glucose control in type 1 diabetes according to the FDA label. The label clearly states: "DAPAGLIFLOZIN TABLETS are not for use to improve blood sugar (glucose) control in people with type 1 diabetes." 2

While dapagliflozin received limited approval in the EU (at 5 mg/day) as an adjunct to insulin for adults with type 1 diabetes who have a BMI ≥27 kg/m² 3, this approval does not extend to the United States.

Efficacy in Type 1 Diabetes

Clinical trials have shown that SGLT2 inhibitors in type 1 diabetes can provide:

• Modest A1C reductions (0.4%)
• Decreased body weight (approximately 5 kg)
• Reduced insulin doses
• Improved blood pressure 1

In the DEPICT-1 and DEPICT-2 trials, dapagliflozin 5 mg/day as an adjunct to insulin improved glycemic control and reduced total daily insulin dose in adults with inadequately controlled type 1 diabetes 4.

Safety Concerns

The major concern limiting use in type 1 diabetes is the significantly increased risk of diabetic ketoacidosis (DKA):

• SGLT2 inhibitor use in type 1 diabetes was associated with an increased rate of DKA 1
• The SGLT1/2 inhibitor sotagliflozin showed an eight-fold increase in DKA compared with placebo 1
• Studies that led to heart failure indications for SGLT2 inhibitors specifically excluded individuals with type 1 diabetes or history of DKA 1

Risk Mitigation

If a clinician were to consider off-label use in very specific circumstances:

1. Patient selection is critical:

   • BMI ≥27 kg/m² (showed lower DKA risk in studies) 4
   • Highly educated on DKA recognition and management
   • No history of DKA
   • Excellent adherence to insulin therapy

2. Monitoring requirements:

   • Regular ketone monitoring
   • Sick day management protocols
   • Immediate access to healthcare
   • Regular follow-up

3. Risk mitigation strategies:

   • Implementation of protocols like the "STOP DKA Protocol" 5
   • Patient education on early DKA recognition
   • Temporary discontinuation during illness, surgery, or reduced food intake

Conclusion

The American Diabetes Association's Standards of Care (2024) does not recommend SGLT2 inhibitors for routine use in type 1 diabetes 1. The FDA label explicitly states that dapagliflozin is not for use in type 1 diabetes 2.

While some limited evidence suggests potential benefits in carefully selected patients, the significant risk of DKA and lack of FDA approval make Farxiga (dapagliflozin) inappropriate for general use in type 1 diabetes. Any consideration for off-label use should involve extensive risk-benefit discussions, implementation of strict risk mitigation strategies, and careful patient selection.