What alternative treatments are available for an elderly patient with Stage 3B Chronic Kidney Disease (CKD), diabetes, and proteinuria, who cannot take Farxiga (dapagliflozin) due to adverse effects?

Alternative SGLT2 Inhibitors and Other Glucose-Lowering Options for Stage 3B CKD with Diabetes and Proteinuria

Primary Recommendation: Switch to Canagliflozin or Empagliflozin

If Farxiga (dapagliflozin) caused intolerable adverse effects, switch to canagliflozin 100 mg once daily as the first alternative SGLT2 inhibitor, as it provides equivalent cardiovascular and renal protection with a potentially different side effect profile. 1

Why Canagliflozin is the Best Alternative

• Canagliflozin can be initiated at eGFR ≥30 mL/min/1.73 m² (Stage 3B CKD qualifies), making it suitable for this patient's renal function. 2

• The CREDENCE trial demonstrated that canagliflozin reduced the composite renal outcome (≥50% eGFR decline, end-stage renal disease, or renal/cardiovascular death) by 30% in patients with diabetic nephropathy and albuminuria, with 99% of participants on background ACE inhibitor or ARB therapy. 1

• Canagliflozin reduced cardiovascular death or heart failure hospitalization by 31% and reduced cardiovascular death, nonfatal MI, or nonfatal stroke by 20% in the CREDENCE population. 2, 1

• The recommended dose is 100 mg once daily for patients with eGFR 30-60 mL/min/1.73 m², with no titration to 300 mg in this renal function range. 1

Empagliflozin as Second Alternative

• Empagliflozin 10 mg once daily can be initiated if eGFR ≥20 mL/min/1.73 m², making it another viable option for Stage 3B CKD. 2, 3

• The EMPA-KIDNEY trial enrolled patients with eGFR 20-45 mL/min/1.73 m² and demonstrated that empagliflozin reduced progression of kidney disease or cardiovascular death by 28% (HR 0.72,95% CI 0.64-0.82, p<0.001). 3

• Empagliflozin reduced hospitalization from any cause by 14% (HR 0.86,95% CI 0.78-0.95, p=0.003) in the EMPA-KIDNEY trial. 3

• The standard dose is 10 mg once daily regardless of eGFR level down to 20 mL/min/1.73 m². 3

Critical Safety Considerations When Switching SGLT2 Inhibitors

Common Pitfalls to Avoid

• Do not assume all SGLT2 inhibitors will cause the same adverse effects—individual patient responses vary, and switching within the class is often successful. 4

• Withhold the new SGLT2 inhibitor at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis. 4, 1

• Assess volume status before initiating any SGLT2 inhibitor and consider reducing concurrent diuretic doses to prevent excessive volume depletion, especially in elderly patients. 4, 5

Monitoring After Switch

• Check eGFR and creatinine within 1-2 weeks after initiating the new SGLT2 inhibitor, as an acute eGFR dip of 3-5 mL/min/1.73 m² is expected and reversible. 4, 5

• If eGFR decreases >30% from baseline AND there are signs of hypovolemia, reduce diuretic doses first before considering SGLT2 inhibitor adjustment. 4

• Continue monitoring eGFR every 3-6 months for Stage 3B CKD. 5

Alternative Non-SGLT2 Inhibitor Options if All SGLT2 Inhibitors Are Contraindicated

GLP-1 Receptor Agonists (Preferred Second-Line)

If all SGLT2 inhibitors are contraindicated or not tolerated, initiate a GLP-1 receptor agonist such as semaglutide or liraglutide, as these provide cardiovascular risk reduction and slow CKD progression without the adverse effects specific to SGLT2 inhibitors. 2

• GLP-1 RAs are recommended for cardiovascular risk reduction if such risk is predominant, as they reduce risks of CVD events and hypoglycemia and slow progression of CKD. 2

• Semaglutide reduced the risk of new or worsening nephropathy (composite of persistent UACR >300 mg/g, doubling of serum creatinine, or ESRD) by 36% (p<0.01). 2

• Liraglutide reduced the risk of new or worsening nephropathy (composite of persistent macroalbuminuria, doubling of serum creatinine, ESRD, or death from ESRD) by 22%. 2

• GLP-1 RAs can be used without dose adjustment in Stage 3B CKD (eGFR 30-44 mL/min/1.73 m²). 2

DPP-4 Inhibitors (Third-Line Option)

• Linagliptin 5 mg once daily requires no dose adjustment regardless of renal function and is the only DPP-4 inhibitor that does not require dose reduction in Stage 3B CKD. 4

• Sitagliptin requires dose reduction to 50 mg once daily if eGFR 30-44 mL/min/1.73 m². 4

• DPP-4 inhibitors have low hypoglycemia risk when combined with metformin but provide minimal cardiovascular or renal protection compared to SGLT2 inhibitors or GLP-1 RAs. 4

Metformin Continuation

• Continue metformin if eGFR ≥30 mL/min/1.73 m², but reassess benefits and risks when eGFR falls to <45 mL/min/1.73 m². 2

• Metformin is contraindicated if eGFR <30 mL/min/1.73 m². 2

• For Stage 3B CKD (eGFR 30-44 mL/min/1.73 m²), reduce metformin to maximum 1000 mg/day. 4

Patient Education Requirements

• Counsel the patient to stop the SGLT2 inhibitor immediately during acute illness (fever, vomiting, diarrhea, reduced oral intake) and contact their healthcare provider. 4

• Educate about genital mycotic infections, which occur in approximately 6% of patients on SGLT2 inhibitors versus 1% on placebo, and emphasize daily hygienic measures. 4

• Instruct the patient to seek immediate medical attention if they develop symptoms of diabetic ketoacidosis (malaise, nausea, vomiting) even with normal blood glucose levels. 4