Can SGLT-1 (sodium-glucose linked transporter 1) inhibitors be used as a treatment for type 1 diabetes?

SGLT-1 Inhibitors in Type 1 Diabetes: Not FDA-Approved and Carry Significant DKA Risk

SGLT-1 inhibitors are not FDA-approved for use in type 1 diabetes and carry a significant risk of diabetic ketoacidosis (DKA), including euglycemic DKA, which outweighs potential benefits in most cases. 1

Current Status and Regulatory Position

• SGLT inhibitors (including SGLT-1, SGLT-2, and dual SGLT-1/2 inhibitors) are not FDA-approved for the treatment of patients with type 1 diabetes, despite showing some glycemic benefits 1
• While sotagliflozin (a dual SGLT-1/2 inhibitor) received approval in the EU for specific type 1 diabetes patients with BMI ≥27 kg/m², it has not received FDA approval in the US 2
• Clinical trials have shown modest benefits, but these are outweighed by safety concerns, particularly the risk of DKA 1

Potential Benefits in Type 1 Diabetes

• Modest improvements in glycemic control with A1C reductions of 0.2-0.5% 3, 4, 5
• Reduction in insulin requirements (approximately 32% reduction in bolus insulin dose in some studies) 4
• Weight loss benefits (1.7 kg reduction compared to 0.5 kg gain with placebo in one study) 4
• Increased time in target glucose range (70-180 mg/dL) 4
• Potential cardio-renal benefits similar to those seen in type 2 diabetes 5

Significant Risks and Concerns

• Increased risk of diabetic ketoacidosis (DKA), including euglycemic DKA (occurring without significantly elevated blood glucose) 1
• DKA risk is 5-17 times higher in type 1 diabetes patients treated with SGLT inhibitors compared to those not on these medications 1
• The FDA has issued a specific warning about the risk of euglycemic DKA with SGLT inhibitors 1
• Up to one-third of DKA cases present with glucose levels <200 mg/dL, making detection challenging 1
• Increased risk of urinary tract infections and pyelonephritis (RR 2.27) compared to other adjunctive therapies 5

Risk Mitigation Strategies

• If considering off-label use (not recommended), implement strict ketone monitoring protocols 1
• Educate patients about signs and symptoms of DKA (dyspnea, nausea, vomiting, abdominal pain) 1
• Instruct patients to immediately stop taking SGLT inhibitors and seek medical attention if DKA symptoms develop 1
• Avoid use during periods of increased DKA risk: illness, reduced food intake, dehydration, alcohol consumption 1
• Consider alternative adjunctive therapies with better safety profiles for type 1 diabetes 1

Alternative Adjunctive Therapies for Type 1 Diabetes

• Pramlintide is FDA-approved for use in adults with type 1 diabetes, with modest A1C reductions (0-0.3%) and weight benefits (1-2 kg) 1
• Metformin may provide small reductions in weight and lipid levels but does not significantly improve A1C in type 1 diabetes 1
• GLP-1 receptor agonists show modest A1C reductions (0.2-0.5%) with significant weight loss benefits (approximately 3 kg) and lower DKA risk compared to SGLT inhibitors 1, 5

Conclusion

Despite potential benefits in glycemic control, insulin dose reduction, and weight management, SGLT-1 inhibitors pose a significant risk of diabetic ketoacidosis in type 1 diabetes patients. Current guidelines and FDA warnings do not support their routine use in type 1 diabetes management, and insulin therapy remains the cornerstone of treatment.