SGLT2 Inhibitor Dosage and Usage in CKD

Introduction to SGLT2 Inhibitors

The American Diabetes Association recommends the use of SGLT2 inhibitors in individuals with eGFR as low as 20 mL/min/1.73 m², based on subgroup analyses from the DAPA-CKD and EMPEROR heart failure trials 3
The maximum dosage of SGLT2 inhibitors for patients with type 2 diabetes and CKD is a fixed dose that does not require titration: dapagliflozin 10 mg once daily, empagliflozin 25 mg once daily (or 10 mg if 25 mg not tolerated), and canagliflozin 100 mg once daily for patients with eGFR 30-60 mL/min/1.73 m² (300 mg daily if eGFR ≥60) 1, 2

For patients with eGFR ≥45 mL/min/1.73 m², initiate dapagliflozin 10 mg once daily for all indications (glycemic control, cardiovascular protection, renal protection), with no dose adjustment needed 1, 2
For patients with eGFR 25-44 mL/min/1.73 m², initiate dapagliflozin 10 mg once daily for cardiovascular/renal protection, but not for glycemic control alone, as glucose-lowering efficacy is significantly reduced at this eGFR range 1, 3
For patients with eGFR 20-24 mL/min/1.73 m², dapagliflozin 10 mg once daily may be initiated for cardiovascular/renal protection based on recent evidence from EMPEROR trials showing safety and efficacy down to eGFR >20 mL/min/1.73 m² 2, 3

For patients with eGFR ≥45 mL/min/1.73 m², initiate empagliflozin 10 mg once daily, which may be increased to 25 mg once daily if additional glycemic control is needed, with a maximum dose of 25 mg once daily 4

For patients with eGFR ≥60 mL/min/1.73 m², initiate canagliflozin 100 mg once daily, which may be increased to 300 mg once daily if additional glycemic control is needed 1, 5
For patients with eGFR 30-59 mL/min/1.73 m², the maximum dose is 100 mg once daily, and the dose should not be exceeded, as the CREDENCE trial demonstrated significant renal and cardiovascular benefits with 100 mg daily in patients with eGFR 30-90 mL/min/1.73 m² 1, 5

For patients with type 2 diabetes and CKD with eGFR 20-44 mL/min/1.73 m² and albuminuria ≥200 mg/g, prioritize dapagliflozin 10 mg once daily, as it has the strongest evidence from the DAPA-CKD trial specifically designed for kidney outcomes in this population 3, 5
For patients with eGFR ≥45 mL/min/1.73 m², any SGLT2 inhibitor can be used at standard doses, with the choice based on formulary, cost, and patient preference 1, 5

Assess volume status before initiating SGLT2 inhibitors, particularly in patients on loop diuretics, elderly patients (≥75 years), or those with low systolic blood pressure, and consider reducing concurrent diuretic doses to prevent excessive volume depletion 1, 2, 5
Withhold SGLT2 inhibitors during acute illness (fever, vomiting, diarrhea, reduced oral intake) and at least 3 days before major surgery or procedures requiring prolonged fasting to prevent euglycemic diabetic ketoacidosis 1, 2
Monitor for genital mycotic infections (which occur in ~6% of patients vs 1% on placebo) and urinary tract infections, and educate patients about symptoms and prevention strategies 1, 2
Recheck eGFR within 1-2 weeks after initiation, then at least every 3-6 months if eGFR 30-59 mL/min/1.73 m², or annually if eGFR ≥60 mL/min/1.73 m² 1, 2