Is it reasonable to discontinue glipizide and Pioglitazone and initiate Farxiga (dapagliflozin) in an elderly patient with Stage 3B Chronic Kidney Disease, diabetes, and proteinuria to reduce cardiovascular risk and slow CKD progression?

Discontinuing Glipizide and Pioglitazone for Farxiga (Dapagliflozin) in Stage 3B CKD

Yes, this is an excellent and evidence-based decision that prioritizes cardiovascular and renal protection over glycemic control alone, particularly given the patient's Stage 3B CKD, diabetes, and proteinuria. 1, 2

Rationale for This Medication Switch

Why Remove Glipizide and Pioglitazone

• Glipizide (sulfonylurea) increases hypoglycemia risk without providing cardiovascular or renal protection, making it inferior to SGLT2 inhibitors in patients with established CKD 2
• Pioglitazone causes fluid retention and weight gain, which can worsen heart failure risk and is particularly problematic in elderly patients with CKD 2
• Neither medication reduces cardiovascular death, heart failure hospitalization, or kidney disease progression—outcomes that are critical in Stage 3B CKD 1, 2

Why Add Farxiga (Dapagliflozin)

The 2024 KDIGO guidelines provide a Class 1A recommendation for treating adults with CKD and eGFR ≥20 mL/min/1.73 m² with an SGLT2 inhibitor when urine albumin-to-creatinine ratio (UACR) ≥200 mg/g or heart failure is present. 1

• Dapagliflozin reduces the primary composite outcome (≥50% sustained eGFR decline, end-stage kidney disease, or renal/cardiovascular death) by 39% (HR 0.61,95% CI 0.51-0.72) in patients with CKD and proteinuria 2, 3
• Kidney-specific benefits include a 44% reduction in sustained eGFR decline ≥50%, end-stage kidney disease, or renal death (HR 0.56,95% CI 0.45-0.68) 2
• Cardiovascular death or heart failure hospitalization is reduced by 29% (HR 0.71,95% CI 0.55-0.92) 2, 3
• All-cause mortality is reduced by 31% (HR 0.69,95% CI 0.53-0.88) 2

Dosing and Administration for Stage 3B CKD

Initiate dapagliflozin 10 mg once daily—this is the fixed dose for cardiovascular and renal protection, with no titration required. 1, 2

• At Stage 3B CKD (eGFR 30-44 mL/min/1.73 m²), dapagliflozin 10 mg daily remains appropriate for cardiovascular and renal protection, though glucose-lowering efficacy will be reduced 2
• Do not reduce the dose based on eGFR alone—the 10 mg dose is used in all major cardiovascular and renal outcome trials 2
• Continue dapagliflozin even if eGFR subsequently falls below 25 mL/min/1.73 m² until dialysis is initiated 1, 2

Critical Safety Precautions Before Initiation

Volume Status Assessment

• Assess volume status before starting dapagliflozin and consider reducing concurrent diuretic doses to prevent excessive volume depletion 1, 2, 4
• Elderly patients and those on loop diuretics are at increased risk for volume depletion and hypotension 4
• Monitor for signs and symptoms of hypotension after initiating therapy 4

Expected eGFR Changes

• An initial eGFR dip of 3-5 mL/min/1.73 m² typically occurs within the first 1-4 weeks, which is transient, reversible, and generally not an indication to discontinue therapy 1, 2
• Check eGFR and creatinine within 1-2 weeks after initiation to document this expected change 2
• This initial decline is actually associated with better long-term renal outcomes 2

Hypoglycemia Risk Management

• Stop glipizide completely when starting dapagliflozin—the combination increases hypoglycemia risk without additional cardiovascular benefit 2
• If the patient is on insulin, consider reducing insulin doses to minimize hypoglycemia risk when adding dapagliflozin 4
• The combination of metformin and dapagliflozin has low hypoglycemia risk and requires no preemptive dose reduction 2

Patient Education Requirements

Sick Day Rules (Critical)

• Instruct the patient to stop dapagliflozin immediately during any acute illness, particularly with fever, vomiting, diarrhea, or reduced food/fluid intake 1, 2, 4
• Withhold dapagliflozin at least 3 days before major surgery or procedures with prolonged fasting to prevent postoperative ketoacidosis 2, 4
• Resume dapagliflozin only after the patient has recovered from acute illness and normal oral intake is re-established 2

Ketoacidosis Warning

• Educate about euglycemic diabetic ketoacidosis (DKA), which can occur even with normal blood glucose levels 2, 4
• Symptoms include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath 4
• Instruct the patient to seek immediate medical attention if these symptoms develop 2, 4

Infection Monitoring

• Genital mycotic infections occur in approximately 6% of patients on SGLT2 inhibitors versus 1% on placebo 2
• Counsel about daily hygienic measures to reduce this risk 2
• Monitor for urinary tract infections and treat promptly if they occur 4

Monitoring Schedule

• Recheck eGFR within 1-2 weeks after initiation, then at least every 3-6 months in Stage 3B CKD 2
• Monitor volume status, blood pressure, and signs of hypotension, especially in the first few weeks 4
• Assess for genital mycotic infections and urinary tract infections at follow-up visits 4

Common Pitfalls to Avoid

• Do not discontinue dapagliflozin solely because eGFR falls below 45 mL/min/1.73 m²—cardiovascular and renal protective benefits persist even when glycemic efficacy is lost 2
• Do not reduce the dapagliflozin dose to 5 mg for cardiovascular/renal protection—all outcome trials used 10 mg daily 2
• Do not continue glipizide "just in case" for glycemic control—the hypoglycemia risk outweighs any marginal glycemic benefit when combined with dapagliflozin 2
• Do not forget to educate about sick day rules—failure to withhold dapagliflozin during illness significantly increases DKA risk 2, 4