Discontinue Glipizide and Initiate Dapagliflozin
Yes, discontinue glipizide 5 mg twice daily and start dapagliflozin (Farxiga) 10 mg once daily—this switch is strongly recommended for a patient with type 2 diabetes, elevated HbA1c, and eGFR 44 mL/min/1.73 m², as dapagliflozin provides superior cardiovascular and renal protection that glipizide cannot offer, and the 10 mg dose is appropriate for cardiorenal protection at this eGFR level. 1, 2, 3
Rationale for Discontinuing Glipizide
Glipizide offers no cardiovascular or renal protection and increases hypoglycemia risk, particularly when combined with other glucose-lowering agents—benefits that are critical in a patient with CKD stage 3b. 1
KDIGO 2020 guidelines explicitly recommend SGLT2 inhibitors as first-line therapy alongside metformin for patients with type 2 diabetes and CKD, with sulfonylureas relegated to "other options" only when preferred agents cannot be used. 1
Stopping glipizide eliminates hypoglycemia risk when initiating dapagliflozin, and the combination of these two agents provides no additive cardiovascular benefit while increasing adverse events. 1, 2
Dapagliflozin Dosing at eGFR 44 mL/min/1.73 m²
Initiate dapagliflozin 10 mg once daily—this is the evidence-based dose for cardiovascular and renal protection in patients with eGFR ≥25 mL/min/1.73 m². 1, 2, 3
Dapagliflozin should NOT be used for glycemic control at eGFR <45 mL/min/1.73 m² because glucose-lowering efficacy is significantly reduced due to its mechanism of action, but the 10 mg dose remains appropriate for cardiorenal protection. 1, 2, 3
The FDA label states: "DAPAGLIFLOZIN TABLETS are not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m². DAPAGLIFLOZIN TABLETS are likely to be ineffective in this setting based upon its mechanism of action." 3
However, the same FDA label approves 10 mg daily for cardiorenal indications: "The recommended dosage of DAPAGLIFLOZIN TABLETS in patients with an eGFR greater than or equal to 25 mL/min/1.73 m² is the same as the recommended dosage in patients with normal renal function" for reducing sustained eGFR decline, ESKD, CV death, and heart failure hospitalization. 3
Evidence-Based Cardiovascular and Renal Benefits
Dapagliflozin reduces the composite outcome of sustained eGFR decline ≥50%, end-stage kidney disease, or renal/cardiovascular death by 39% (HR 0.61,95% CI 0.51–0.72) in patients with CKD and albuminuria. 2
The kidney-specific composite outcome is reduced by 44% (HR 0.56,95% CI 0.45–0.68), demonstrating robust renal protection. 2
Cardiovascular death or heart failure hospitalization is reduced by 29% (HR 0.71,95% CI 0.55–0.92), and all-cause mortality by 31% (HR 0.69,95% CI 0.53–0.88). 2
These benefits are consistent regardless of diabetes status—67.5% of DAPA-CKD participants had type 2 diabetes and 32.5% did not, with similar effect sizes in both subgroups. 2
Practical Implementation Algorithm
Step 1: Pre-Initiation Assessment
- Check eGFR (already 44 mL/min/1.73 m²—appropriate for initiation). 1, 3
- Assess volume status—correct any volume depletion before starting dapagliflozin, and consider reducing concurrent diuretic doses if the patient is on loop or thiazide diuretics. 1, 2, 3
- Exclude contraindications: pregnancy, breastfeeding, dialysis, or history of serious hypersensitivity to dapagliflozin. 3
Step 2: Medication Adjustments
- Stop glipizide 5 mg BID completely when starting dapagliflozin—do not taper, as the combination increases hypoglycemia risk without additional benefit. 1, 2
- Continue metformin if the patient is on it and eGFR is ≥30 mL/min/1.73 m²; at eGFR 30–44 mL/min/1.73 m², reduce metformin to a maximum of 1000 mg/day. 1
- Start dapagliflozin 10 mg once daily—no titration is required; this is the fixed dose for all cardiorenal indications. 2, 4, 3
Step 3: Monitoring
- Recheck eGFR within 1–2 weeks after initiation—an acute, reversible eGFR dip of 2–5 mL/min/1.73 m² is expected and should NOT prompt discontinuation. 1, 2
- Monitor glucose closely for the first 2–4 weeks, especially if the patient is on insulin or other glucose-lowering agents. 1, 2
- Assess volume status at follow-up, particularly in elderly patients or those on diuretics. 1, 2, 3
Step 4: Patient Education
- Counsel about genital mycotic infections (occur in ~6% of patients vs. 1% with placebo)—emphasize daily hygiene. 1, 2
- Warn about euglycemic diabetic ketoacidosis—advise immediate medical evaluation for malaise, nausea, vomiting, or abdominal pain even when blood glucose is normal. 1, 2
- Instruct to withhold dapagliflozin during acute illness with reduced oral intake, fever, vomiting, or diarrhea, and to stop at least 3 days before major surgery or procedures requiring prolonged fasting. 1, 2, 3
Common Pitfalls to Avoid
Do NOT discontinue dapagliflozin when eGFR falls below 45 mL/min/1.73 m²—cardiovascular and renal benefits persist even when glycemic efficacy is lost. 1, 2
Do NOT stop dapagliflozin because of the expected initial eGFR dip in the first 2–4 weeks—this hemodynamic change is reversible and does not indicate kidney injury. 1, 2
Do NOT reduce the dose below 10 mg for cardiovascular or renal indications, even if glycemic efficacy wanes at lower eGFR—all outcome trials used the fixed 10 mg dose. 2, 4
Do NOT combine dapagliflozin with glipizide—the combination increases hypoglycemia risk without additional cardiovascular benefit. 1, 2
Additional Glycemic Management if Needed
If additional glucose-lowering is required after stopping glipizide, consider a GLP-1 receptor agonist (liraglutide, dulaglutide, or semaglutide), which can be used at eGFR >30 mL/min/1.73 m² without dose adjustment and provides additional cardiovascular benefits. 1
Insulin remains effective regardless of kidney function and should be the primary glucose-lowering agent if aggressive glycemic control is needed. 1
DPP-4 inhibitors (e.g., linagliptin) require no dose adjustment at any eGFR level and can be considered, though they lack the cardiovascular and renal benefits of SGLT2 inhibitors and GLP-1 receptor agonists. 1