What is the recommended approach for initiating SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors in patients?

Recommended Approach for Initiating SGLT2 Inhibitors in Patients

SGLT2 inhibitors should be initiated in most patients with type 2 diabetes and chronic kidney disease with eGFR ≥20 mL/min/1.73 m² independent of HbA1c or the need for additional glucose lowering. 1

Patient Selection

Eligibility Criteria:

• eGFR ≥20 mL/min/1.73 m² (minimum threshold for initiation) 1
• High priority for patients with:
  • Albuminuria (ACR ≥200 mg/g) 1
  • Heart failure 1
  • Established atherosclerotic cardiovascular disease 1

Contraindications:

• Pregnancy or breastfeeding 2
• eGFR <20 mL/min/1.73 m² 1
• Kidney transplant recipients (due to immunosuppression) 3
• Active genital infections 3

Initiation Protocol

Step 1: Pre-initiation Assessment

• Measure baseline eGFR and albuminuria 3
• Assess volume status and risk for volume depletion 1
• Evaluate hypoglycemia risk (especially if on insulin or sulfonylureas) 1
• Check for foot ulcers or active infections 1

Step 2: Select Appropriate SGLT2 Inhibitor

• Preferred agents with proven cardiovascular and renal benefits:
  • Canagliflozin 100 mg daily 1
  • Dapagliflozin 10 mg daily 1
  • Empagliflozin 10 mg daily 1

Step 3: Medication Adjustments

• If patient is on insulin or sulfonylureas:
  • Reduce sulfonylurea dose by 50% or discontinue if on minimal dose 1
  • Reduce total daily insulin dose by approximately 20% 1
• If patient is on diuretics:
  • Consider reducing diuretic dose to prevent excessive volume depletion 1

Step 4: Patient Education

• Provide guidance on:
  • Genital hygiene to prevent mycotic infections 1
  • Recognition of diabetic ketoacidosis symptoms 1
  • Volume depletion symptoms 1
  • "Sick day protocol" (temporarily withhold SGLT2i during illness, maintain hydration) 1

Monitoring

Short-term Follow-up (2-4 weeks):

• Monitor for initial eGFR "dip" of 3-5 mL/min/1.73 m² (hemodynamic and generally reversible) 3
• Assess for hypoglycemia if on insulin or sulfonylureas 1
• Check for signs of volume depletion 1

Long-term Follow-up:

• Monitor kidney function periodically, with frequency based on baseline eGFR 1, 3
• Assess for genital mycotic infections 1
• Continue to monitor glycemic control 1

Special Considerations

Renal Function:

• The glucose-lowering effect diminishes with declining kidney function 3
• Benefits for cardiovascular and kidney outcomes persist even with minimal glycemic effects 3
• Once initiated, SGLT2 inhibitors can be continued at lower eGFR levels 1

Perioperative Management:

• Withhold SGLT2 inhibitor the day of day-stay procedures 1
• For major procedures requiring hospitalization, withhold at least 2 days in advance 1
• Resume after recovery from procedure 1

Common Pitfalls and Caveats

1. Misinterpreting initial eGFR decline: The initial 3-5 mL/min/1.73 m² decrease in eGFR is hemodynamic and generally not a reason to discontinue therapy 3

2. Inadequate dose adjustment of concomitant medications: Failing to reduce insulin or sulfonylurea doses can lead to hypoglycemia 1

3. Overlooking risk of euglycemic diabetic ketoacidosis: This rare but serious adverse effect requires prompt recognition, especially during illness or fasting 1

4. Continuing during acute illness: SGLT2 inhibitors should be temporarily withheld during acute illness with risk of dehydration 3

5. Initiating below recommended eGFR threshold: Starting SGLT2 inhibitors when eGFR <20 mL/min/1.73 m² is not recommended due to limited efficacy and safety data 1

By following this structured approach to SGLT2 inhibitor initiation, clinicians can optimize the cardiorenal benefits while minimizing potential adverse effects in patients with type 2 diabetes.