How to manage a patient with Chronic Kidney Disease (CKD) grade 3 and uncontrolled hyperglycemia on Mixtard (Insulin) 22 and 16?

Management of Uncontrolled Diabetes in CKD Stage 3 on Mixtard

Immediately reduce your patient's total daily insulin dose by 40-50% (from 38 units to approximately 20 units daily) and switch from Mixtard to a basal-bolus regimen using long-acting basal insulin plus rapid-acting mealtime insulin, while simultaneously adding an SGLT2 inhibitor for cardiorenal protection. 1

Immediate Insulin Regimen Changes

The current Mixtard regimen (22 units morning, 16 units evening) is dangerous in CKD stage 3 and must be changed immediately. 1 Premixed insulin formulations like Mixtard create unacceptably high hypoglycemia risk because CKD stage 3 simultaneously increases insulin resistance while impairing renal insulin clearance, prolonging insulin half-life by approximately one-third. 2, 1

Recommended New Insulin Regimen:

• Start long-acting basal insulin (glargine or detemir) 10 units once daily at bedtime 1
• Add rapid-acting insulin (lispro, aspart, or glulisine) 2-3 units before each main meal 1
• This brings total daily dose to approximately 16-19 units (a 50% reduction from current 38 units) 1

The basal-bolus approach provides superior glycemic control with significantly lower hypoglycemia risk compared to premixed insulin in CKD patients. 1

Glycemic Target Modification

Target HbA1c of 7-8% for this patient, NOT the standard <7%. 2, 1 The KDOQI and KDIGO guidelines specifically endorse this higher target for patients with CKD stage 3 and high comorbidity burden. 2 Targeting HbA1c <7% in CKD with insulin increases mortality risk without providing additional microvascular benefit. 1

Patients with CKD stage 3 have a 5-fold increased risk of severe hypoglycemia when treated intensively with insulin. 2 The risk of hypoglycemia-related harm outweighs potential benefits of tighter control at this stage of kidney disease. 1

Add SGLT2 Inhibitor Immediately

Start empagliflozin 10 mg daily or dapagliflozin 10 mg daily regardless of current glucose control. 2, 1, 3 This is critical because SGLT2 inhibitors provide cardiorenal protection independent of their glucose-lowering effects in CKD stage 3. 2, 1

• SGLT2 inhibitors reduce cardiovascular events and slow CKD progression even when glycemic targets are already met 2
• They can be continued even if eGFR falls below 30 mL/min/1.73 m² once initiated 2
• When adding SGLT2 inhibitors to insulin, reduce insulin doses by 10-20% to prevent hypoglycemia 2

Do not wait for "inadequate glycemic control" to add SGLT2 inhibitors—their primary benefit in CKD is cardiorenal protection, not glucose lowering. 1

Intensive Glucose Monitoring Protocol

Implement 4-times-daily glucose monitoring (before each meal and at bedtime) for the first 2-4 weeks after changing the insulin regimen. 1 This is non-negotiable to prevent life-threatening hypoglycemia during the transition period. 1

• Check HbA1c every 3 months, but recognize it may underestimate glycemia if anemia is present from CKD 2, 1
• Consider continuous glucose monitoring (CGM) if available, as it provides superior hypoglycemia detection and is unaffected by renal function 2, 1
• If CGM is used, target time-in-range of 50-70% rather than focusing solely on HbA1c 2

HbA1c accuracy declines with CKD stage 3 due to anemia, altered red blood cell lifespan, and potential erythropoietin use. 2

Consider GLP-1 Receptor Agonist

If glycemic control remains inadequate after optimizing insulin and adding SGLT2 inhibitor, add a long-acting GLP-1 receptor agonist (dulaglutide or semaglutide). 2, 4 These agents:

• Reduce cardiovascular events in high-risk patients 2
• Preserve eGFR and reduce albuminuria 2
• Have minimal hypoglycemia risk when combined with basal insulin 2
• Require no dose adjustment in CKD stage 3 4

Medication Adjustments Based on eGFR

For CKD stage 3 (eGFR 30-59 mL/min/1.73 m²):

• Metformin: Continue if eGFR ≥30, discontinue if eGFR <30 2, 3
• Sulfonylureas: Avoid entirely or use only glipizide/gliclazide at reduced doses 2 First-generation sulfonylureas (chlorpropamide, tolbutamide) are absolutely contraindicated 2
• SGLT2 inhibitors: Safe to initiate and continue 2, 3
• GLP-1 agonists: No dose adjustment needed 2, 4

Critical Safety Measures

Educate the patient on hypoglycemia symptoms and treatment immediately. 4 Hypoglycemia awareness may be impaired in CKD, making patient education essential. 4

Reassess insulin requirements every 3-6 months as kidney function may continue to decline. 1, 4 Stable insulin requirements should never be assumed in progressive CKD. 1

During acute illness, temporarily hold insulin or reduce doses by an additional 20-30%. 4 Decreased oral intake during illness combined with impaired renal insulin clearance creates extreme hypoglycemia risk. 2

Common Pitfalls to Avoid

• Never continue Mixtard or other premixed insulin in CKD stage 3—the fixed ratio prevents appropriate dose adjustments and dramatically increases hypoglycemia risk 1
• Never target HbA1c <6.5% with insulin in CKD stage 3—this increases hypoglycemia-related hospitalization and mortality without benefit 1
• Never delay SGLT2 inhibitor initiation—cardiorenal protection is independent of glucose lowering and should begin immediately 1
• Never use HbA1c alone for monitoring—supplement with frequent glucose checks or CGM due to reduced HbA1c reliability in CKD 2, 1
• Never assume the patient understands hypoglycemia management—impaired awareness is common in CKD and requires explicit education 4

Monitoring Schedule

Week 1-2: Daily glucose checks 4 times daily, adjust rapid-acting insulin by 1-2 units every 3 days based on patterns 1, 4

Week 3-4: Continue 4-times-daily monitoring, adjust basal insulin by 1-2 units every 3-5 days if fasting glucose remains elevated 4

Month 2-3: Reduce to 2-3 times daily monitoring if stable, check HbA1c at 3 months 2

Ongoing: HbA1c every 3 months, reassess insulin requirements every 3-6 months, monitor eGFR and adjust medications accordingly 1, 4