Use of Dapagliflozin in Type 1 Diabetes Mellitus
Dapagliflozin should not be used in patients with Type 1 Diabetes Mellitus due to a significantly increased risk of diabetic ketoacidosis (DKA), which can be life-threatening. 1
Safety Concerns for Type 1 DM Patients
The FDA label explicitly states that dapagliflozin significantly increases the risk of diabetic ketoacidosis beyond the background rate in patients with Type 1 diabetes 1. This warning is clear and definitive:
- Dapagliflozin is not indicated for glycemic control in patients with Type 1 diabetes mellitus
- In placebo-controlled trials, the risk of ketoacidosis was markedly increased in patients with Type 1 diabetes who received SGLT2 inhibitors
- There have been postmarketing reports of fatal events of ketoacidosis in patients using SGLT2 inhibitors
Risk of Diabetic Ketoacidosis
The risk of DKA is particularly concerning in Type 1 diabetes patients:
- Clinical trials showed that patients with Type 1 diabetes using dapagliflozin had a 4.0% incidence of definite DKA compared to 1.9% with placebo 2
- DKA may present atypically as euglycemic ketoacidosis (blood glucose <250 mg/dL), making it harder to detect 3
- Precipitating factors for DKA include:
- Under-insulinization due to insulin dose reduction
- Missed insulin doses
- Acute febrile illness
- Reduced caloric intake
- Surgery
- Volume depletion
- Alcohol abuse
European Regulatory Status
While the FDA has not approved dapagliflozin for Type 1 diabetes, it's worth noting that the European Medicines Agency (EMA) has approved dapagliflozin at a dosage of 5 mg/day as an adjunct to insulin in a specific subset of adults with Type 1 diabetes 4:
- Only for adults with BMI ≥27 kg/m²
- Only when insulin alone does not provide adequate glycemic control despite optimal insulin therapy
- With strict risk mitigation measures for DKA
However, this European approval does not override the safety concerns identified in clinical trials and reflected in the FDA labeling.
Alternative Approaches for Type 1 Diabetes
For patients with Type 1 diabetes requiring improved glycemic control:
- Optimize insulin therapy (basal-bolus regimens or insulin pump therapy)
- Consider continuous glucose monitoring
- Focus on lifestyle modifications (diet, exercise, stress management)
- Ensure proper diabetes education and self-management training
Conclusion
Based on the FDA labeling and safety data, dapagliflozin should not be used in patients with Type 1 diabetes mellitus due to the significantly increased risk of diabetic ketoacidosis, which can be life-threatening and may present atypically with near-normal blood glucose levels.