Add Basal Insulin to Achieve Glycemic Control
For this patient with CKD stage 4 (eGFR 24) and uncontrolled diabetes (A1c 9.4%) already on maximum doses of semaglutide and dapagliflozin, add basal insulin as the next agent to achieve glycemic control. 1
Current Medication Assessment
Your patient is already on appropriate foundational therapy:
- Semaglutide (Ozempic) 1 mg weekly: This GLP-1 receptor agonist is safe and effective at eGFR 24, with recent evidence showing significant renal and cardiovascular benefits in advanced CKD 2, 3, 4
- Dapagliflozin 10 mg daily: While FDA-approved down to eGFR 25 for cardiorenal protection, this SGLT2 inhibitor provides minimal glucose-lowering efficacy at eGFR 24 due to reduced renal glucose filtration 5, 6
Why Basal Insulin is the Correct Next Step
The KDIGO 2020 guidelines explicitly recommend adding insulin when glycemic targets are not achieved despite metformin, SGLT2 inhibitor, and GLP-1 receptor agonist therapy. 1 With an A1c of 9.4%, this patient requires additional glucose-lowering beyond what the current regimen provides.
Key Considerations at eGFR 24:
- Metformin is contraindicated: Must be discontinued at eGFR <30 due to lactic acidosis risk 1
- SGLT2 inhibitors lose glucose-lowering efficacy: At eGFR 24, dapagliflozin provides cardiorenal protection but minimal glycemic benefit 5, 6
- GLP-1 RA efficacy is maintained: Semaglutide remains effective and safe at this level of renal function 2, 3, 4
- DPP-4 inhibitors are insufficient: These agents reduce A1c by only 0.4-0.9%, inadequate for an A1c of 9.4% 7
Specific Insulin Recommendation
Start with basal insulin (NPH, glargine, or detemir) at 10 units once daily at bedtime or 0.1-0.2 units/kg/day. 1
Titration Protocol:
- Increase by 2-4 units every 3 days based on fasting glucose readings 1
- Target fasting glucose: 80-130 mg/dL 1
- Monitor for hypoglycemia, which occurs more frequently in CKD due to reduced insulin clearance 1
Continue Current Medications
Do not discontinue dapagliflozin despite limited glucose-lowering at this eGFR. 5 The FDA label specifically states that patients may continue dapagliflozin 10 mg daily even if eGFR falls below 25 to reduce risk of eGFR decline, ESKD, cardiovascular death, and heart failure hospitalization 5.
Continue semaglutide 1 mg weekly. 2, 4 The recent FLOW trial demonstrated that semaglutide reduced major kidney disease events by 24% and cardiovascular death by 29% in patients with eGFR as low as 25 4.
Why Not DPP-4 Inhibitors
While DPP-4 inhibitors (linagliptin or dose-adjusted sitagliptin) are options at eGFR 24 7, 8, they would be inadequate as monotherapy add-on:
- Maximum A1c reduction of 0.4-0.9% 7
- Your patient needs approximately 2.4% A1c reduction to reach target
- No cardiovascular or renal benefits demonstrated 7
- Inferior to insulin for achieving glycemic control in advanced CKD 1
DPP-4 inhibitors could be considered only if the patient refuses insulin or experiences recurrent severe hypoglycemia with insulin. 7, 8
Monitoring Requirements
- Check A1c in 3 months to assess response 1
- Monitor eGFR and potassium given advanced CKD 1
- Self-monitor blood glucose at least before breakfast and bedtime initially 1
- Assess for hypoglycemia symptoms at each visit, as insulin clearance is reduced in CKD 1
Critical Pitfall to Avoid
Do not add sulfonylureas in advanced CKD. These agents carry high hypoglycemia risk due to accumulation of active metabolites with reduced renal clearance and should be avoided at eGFR <30 1.