When to start a Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitor, such as canagliflozin (canagliflozin), on a patient with Chronic Kidney Disease (CKD) stage 3b?

When to Start an SGLT2 Inhibitor in a Patient with CKD Stage 3b

SGLT2 inhibitors should be initiated in patients with CKD stage 3b (eGFR 30-44 mL/min/1.73 m²) immediately upon diagnosis, regardless of diabetes status, as they provide significant kidney and cardiovascular protection. 1

Indications for SGLT2 Inhibitors in CKD Stage 3b

For Patients with Type 2 Diabetes:

• Start SGLT2 inhibitor in all patients with T2D and CKD stage 3b (eGFR 30-44 mL/min/1.73 m²) 1
• No need to wait for further kidney function decline or specific albuminuria threshold
• Benefits extend beyond glycemic control to include kidney protection and cardiovascular risk reduction

For Patients without Diabetes:

• Start SGLT2 inhibitor if:
  • eGFR 30-44 mL/min/1.73 m² with urine ACR ≥200 mg/g (≥20 mg/mmol) 1
  • Heart failure is present, regardless of albuminuria level 1
• Consider in patients with urine ACR <200 mg/g (<20 mg/mmol) as well (2B recommendation) 1

Medication Selection and Dosing for CKD Stage 3b

SGLT2 Inhibitor	Dosing in CKD Stage 3b	Notes
Canagliflozin	Maximum 100 mg daily	Can continue if tolerated until dialysis [1]
Dapagliflozin	10 mg daily	Can continue if tolerated until dialysis [1]
Empagliflozin	10 mg daily	Not recommended with eGFR <45 mL/min/1.73 m² [1,2]
Ertugliflozin	Not recommended	Not recommended with eGFR <45 mL/min/1.73 m² [1,2]

Monitoring After Initiation

1. Initial follow-up: Check volume status and glycemia within 2-4 weeks 1

2. eGFR monitoring:

   • Expect a small, reversible decrease in eGFR upon initiation
   • This initial decline is not a reason to discontinue therapy 1
   • No need to alter the frequency of routine CKD monitoring 1

3. Safety monitoring:

   • Monitor for genital mycotic infections (more common in women) 1
   • Watch for signs of euglycemic ketoacidosis, especially in insulin users 1
   • Assess for volume depletion, particularly in elderly or those on diuretics

Continuation of Therapy

• Once initiated, continue SGLT2 inhibitor even if eGFR falls below 20 mL/min/1.73 m² 1
• Only discontinue if:
  • Patient initiates kidney replacement therapy 1
  • Medication is not tolerated 1
  • During periods of acute illness, surgery, or critical medical illness (temporarily) 1

Clinical Benefits in CKD Stage 3b

Research specifically in CKD stage 3b patients demonstrates:

• HbA1c reduction of approximately 0.43% 3
• Weight reduction of 1.6-1.9% 4
• Systolic blood pressure reduction of 2.8-4.4 mmHg 4
• Albuminuria reduction of approximately 20% 3
• Slowed trajectory of kidney function decline 5

Common Pitfalls to Avoid

1. Delaying initiation: Many clinicians hesitate to start SGLT2 inhibitors in reduced kidney function, but evidence supports early initiation for kidney protection 5

2. Stopping due to initial eGFR dip: The initial decline in eGFR is hemodynamic, not a sign of kidney injury, and typically stabilizes over time 4

3. Inadequate patient education: Patients should be instructed to:

   • Maintain adequate hydration
   • Practice good genital hygiene to prevent infections
   • Temporarily hold medication during acute illness
   • Monitor for signs of ketoacidosis if on insulin

4. Failure to adjust concomitant medications: Consider reducing doses of:

   • Diuretics if at risk for volume depletion
   • Insulin or sulfonylureas to prevent hypoglycemia

5. Not continuing despite eGFR decline: Guidelines clearly support continuing SGLT2 inhibitors even as kidney function declines below the initial threshold for starting therapy 1