What are the latest guidelines for using SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors, such as canagliflozin (Canagliflozin), dapagliflozin (Dapagliflozin), or empagliflozin (Empagliflozin), in patients with Chronic Kidney Disease (CKD) and how are they titrated?

SGLT2 Inhibitors for CKD: Latest Guidelines and Titration

Initiate SGLT2 inhibitors at 10 mg daily in all patients with CKD and eGFR ≥20 mL/min/1.73 m² for kidney and cardiovascular protection, regardless of diabetes status or glycemic control—no dose titration is required or recommended. 1

Initiation Criteria

Start SGLT2 inhibitors when eGFR ≥20 mL/min/1.73 m², representing a major shift from previous thresholds of ≥25-30 mL/min/1.73 m². 1 This recommendation applies to:

• Patients with type 2 diabetes and CKD (Grade 1A recommendation) 1
• Patients without diabetes who have CKD (evidence from DAPA-CKD trial) 1, 2
• Highest priority for patients with albuminuria ≥200 mg/g (≥20 mg/mmol), though benefit extends to those with normal albumin excretion 1, 3

The indication is for kidney and cardiovascular protection, not glycemic control—add SGLT2 inhibitors even if HbA1c targets are already met. 1

Dosing: No Titration Required

There is no dose titration for SGLT2 inhibitors in CKD. The approach differs fundamentally from other medications:

Standard Dosing

• Dapagliflozin: 10 mg once daily 4, 5
• Empagliflozin: 10 mg once daily (can increase to 25 mg for additional glycemic control in diabetes, but 10 mg provides full kidney/cardiovascular protection) 1
• Canagliflozin: 100 mg once daily 1

For glycemic control specifically in diabetes without other indications, dapagliflozin may start at 5 mg daily and increase to 10 mg if needed. 5 However, for CKD protection, start directly at 10 mg daily. 4

Critical Point on eGFR and Dosing

Do not adjust the dose based on eGFR decline. 1 The glucose-lowering effect diminishes as eGFR falls, but the kidney and cardiovascular protective effects persist independently of glycemic effects. 1, 6

Continuation Strategy

Once initiated, continue SGLT2 inhibitors even if eGFR falls below 20 mL/min/1.73 m² until kidney replacement therapy begins or the drug is not tolerated. 1, 7 This represents a paradigm shift—the drug is continued for ongoing protection despite loss of glycemic efficacy at very low eGFR.

Pre-Initiation Assessment and Risk Mitigation

Before starting, address these specific issues:

Volume Status

• Reduce or discontinue loop/thiazide diuretics in patients at risk for hypovolemia before starting SGLT2 inhibitors 1
• Counsel patients about symptoms of volume depletion and hypotension 1
• Follow up on volume status after initiation 1

Expected eGFR Changes

• Anticipate a reversible 3-5 mL/min/1.73 m² decline in eGFR within the first 4 weeks—this is hemodynamic, not nephrotoxic, and is not an indication to discontinue therapy 1, 4
• This acute dip reflects reduced intraglomerular pressure (the mechanism of long-term protection) 8

Sick Day Protocol

• Withhold SGLT2 inhibitors during prolonged fasting, surgery, or critical illness when patients are at greater risk for ketosis 1, 5
• Institute a sick day protocol for temporary discontinuation during acute illness 1, 4

Agent Selection

Prioritize agents with documented kidney or cardiovascular benefits: 1

• Dapagliflozin: Proven in DAPA-CKD trial for CKD with or without diabetes; 39% risk reduction in primary kidney outcome 1, 4
• Empagliflozin: Proven in EMPA-KIDNEY trial; effective down to eGFR 20 mL/min/1.73 m² 1, 7
• Canagliflozin: Proven in CREDENCE trial for diabetic kidney disease; 32% risk reduction for ESKD 1

All three agents show consistent efficacy across eGFR ranges studied. 4, 6

Combination Therapy

SGLT2 inhibitors should be added to, not substituted for, existing therapies:

• Continue RAS inhibitors (ACE-I/ARB) as background therapy 1, 4
• Can add nonsteroidal MRA (finerenone) for patients with persistent albuminuria ≥30 mg/g despite maximal RAS inhibition and SGLT2 inhibitor use 1, 3
• Can combine with GLP-1 receptor agonists for additional cardiovascular protection in diabetes 1, 8

Monitoring After Initiation

• Check eGFR and potassium 1-2 weeks after starting, then as clinically indicated 1
• Monitor for genital mycotic infections (6% vs 1% placebo)—counsel on proper hygiene 1, 3, 4
• Do not discontinue for the expected acute eGFR dip unless eGFR falls precipitously beyond the expected 3-5 mL/min/1.73 m² decline 1, 4

Contraindications and Exceptions

Do not use in:

• Kidney transplant recipients—inadequately studied in immunosuppressed patients at increased infection risk 1
• Polycystic kidney disease—not expected to be effective 1, 5
• Patients requiring immunosuppression for kidney disease—not expected to be effective 1, 5
• History of serious hypersensitivity to the specific SGLT2 inhibitor 5

Common Pitfalls to Avoid

1. Do not wait for albuminuria to develop—benefit extends to patients with normal albumin excretion, though strongest evidence is for ACR ≥200 mg/g 1, 3

2. Do not discontinue when eGFR drops acutely after initiation—the initial 3-5 mL/min/1.73 m² decline is expected and beneficial 1, 4

3. Do not withhold because "eGFR is too low for glucose-lowering"—the indication is kidney/cardiovascular protection, not glycemic control 1

4. Do not titrate the dose based on eGFR—use the standard protective dose (10 mg for dapagliflozin/empagliflozin, 100 mg for canagliflozin) regardless of kidney function 4, 5

5. Do not stop when eGFR falls below 20 mL/min/1.73 m² during treatment—continue until dialysis or transplant 1, 7