Discontinue Glipizide and Continue Dapagliflozin for Cardiorenal Protection
You should immediately stop glipizide and continue dapagliflozin 10 mg daily, because at eGFR 24 mL/min/1.73 m² the SGLT2 inhibitor provides critical cardiovascular and renal protection (39% reduction in kidney failure, 29% reduction in CV death/heart failure hospitalization) while glipizide offers no such benefit and substantially increases hypoglycemia risk in advanced CKD. 1, 2
Why Glipizide Must Be Stopped
Sulfonylureas provide zero cardiovascular or renal protection in patients with CKD, unlike SGLT2 inhibitors which reduce major adverse kidney events by 44% and all-cause mortality by 31%. 1, 2, 3
Glipizide dramatically increases hypoglycemia risk in CKD stage 4 because reduced renal clearance of active metabolites causes drug accumulation, and this risk is compounded when combined with dapagliflozin. 4, 5
The 2024 KDIGO guideline explicitly relegates sulfonylureas to "other options" only when SGLT2 inhibitors and GLP-1 receptor agonists cannot be used, giving metformin plus SGLT2 inhibitors a Grade 1A recommendation as first-line therapy. 1
Your patient's A1c rose from 6.6% to 7.4% despite glipizide, demonstrating that the sulfonylurea is failing to provide adequate glycemic control while exposing the patient to unnecessary hypoglycemia risk. 5
Why Dapagliflozin Must Be Continued at eGFR 24
The 2024 KDIGO guideline (the most recent and highest-quality evidence) gives a Grade 1A recommendation to continue SGLT2 inhibitors even when eGFR falls below 25 mL/min/1.73 m² after initiation, because cardiovascular and renal benefits persist until dialysis. 1, 4
In the DAPA-CKD trial, patients with baseline eGFR as low as 25 mL/min/1.73 m² experienced a 39% reduction in the composite of sustained eGFR decline ≥50%, end-stage kidney disease, or cardiovascular/renal death (HR 0.61,95% CI 0.51–0.72). 2, 3
Dapagliflozin reduced cardiovascular death or heart failure hospitalization 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) in patients with advanced CKD. 2, 3
Although dapagliflozin loses most glucose-lowering efficacy when eGFR <45 mL/min/1.73 m², its hemodynamic and anti-inflammatory mechanisms continue to slow CKD progression and lower cardiovascular mortality at eGFR 24. 4, 6, 7
Do not reduce the dapagliflozin dose below 10 mg; all outcome trials demonstrating mortality benefit used this fixed dose regardless of eGFR level. 4, 2
Addressing the Rising A1c Without Glipizide
Add a GLP-1 receptor agonist (semaglutide, dulaglutide, or liraglutide) for additional glycemic control, because these agents provide cardiovascular protection, require no renal dose adjustment, and carry minimal hypoglycemia risk even at eGFR 24. 1, 5
GLP-1 receptor agonists are the preferred third-line agents after metformin and SGLT2 inhibitors according to the 2020 KDIGO guideline (Grade 1B recommendation), and they retain full glucose-lowering potency in advanced CKD. 1
If GLP-1 receptor agonists are contraindicated or not tolerated, use insulin as the primary glucose-lowering agent, because insulin remains effective at any eGFR level and can be dose-titrated based on clinical response. 4, 5
DPP-4 inhibitors (linagliptin requires no dose adjustment) are an alternative if GLP-1 receptor agonists and insulin cannot be used, though they lack the robust cardiorenal benefits of SGLT2 inhibitors and GLP-1 receptor agonists. 4, 5
Critical Safety Monitoring After Stopping Glipizide
Monitor blood glucose closely for the first 2–4 weeks after discontinuing glipizide, because removing the sulfonylurea will eliminate its hypoglycemia risk but may initially raise glucose levels until the GLP-1 receptor agonist or insulin is titrated. 4, 5
Re-measure eGFR and serum creatinine every 3–6 months (or more frequently if clinically indicated) to track kidney function trajectory and ensure dapagliflozin continuation remains appropriate. 4, 5
Temporarily hold dapagliflozin during acute illnesses with reduced oral intake, fever, vomiting, or diarrhea to prevent volume depletion and euglycemic diabetic ketoacidosis, and stop it at least 3 days before major surgery. 4, 5
Educate the patient that genital mycotic infections occur in roughly 6% of dapagliflozin users versus 1% with placebo, and emphasize daily hygiene to reduce this risk. 4, 5
Warn about euglycemic diabetic ketoacidosis and instruct the patient to seek immediate care for unexplained malaise, nausea, vomiting, or abdominal pain even when blood glucose is normal. 4, 5
Common Pitfalls to Avoid
Do not stop dapagliflozin solely because eGFR is 24 mL/min/1.73 m²; the 2024 KDIGO guideline explicitly states that cardiorenal benefits persist despite loss of glycemic efficacy, and continuation is recommended until dialysis. 1, 4
Do not combine dapagliflozin with glipizide, because this combination raises hypoglycemia risk without adding cardiovascular benefit, and sulfonylureas should be discontinued when SGLT2 inhibitors are used. 4, 5
Do not discontinue dapagliflozin in response to the expected initial eGFR dip of 2–5 mL/min/1.73 m² that may occur in the first 2–4 weeks; this hemodynamic change is reversible and does not indicate kidney injury. 4, 7
Do not restart glipizide if A1c remains elevated after stopping it; instead, add a GLP-1 receptor agonist or insulin to achieve glycemic targets while preserving the cardiorenal protection from dapagliflozin. 1, 5