What is the role of glargine (insulin glargine) in patients with Chronic Kidney Disease (CKD)?

Role of Insulin Glargine in Patients with Chronic Kidney Disease

Insulin glargine is an effective and safe option for glycemic control in patients with chronic kidney disease (CKD), with evidence supporting its use across all stages of CKD due to its favorable efficacy and reduced risk of nocturnal hypoglycemia compared to NPH insulin. 1

Insulin Management in CKD

General Considerations

• In CKD, insulin clearance is reduced due to decreased renal function, which may increase the risk of hypoglycemia
• Insulin doses often need to be decreased as kidney function declines due to reduced insulin clearance 2
• For patients with Type 1 diabetes and CKD, insulin remains the only approved therapy 2

Insulin Glargine Efficacy in CKD

• Clinical studies demonstrate that insulin glargine provides effective glycemic control across all stages of CKD:
  • Achieves approximately 1.2% (13.2 mmol/mol) HbA1c reduction in both moderate (Stage 3) and severe (Stage 4) CKD 3
  • Produces significant reductions in fasting and postprandial glucose values without significant weight changes 3
  • Maintains efficacy across different CKD stages with appropriate dose adjustments 4

Safety Profile in CKD

• Insulin glargine shows a favorable safety profile in CKD patients:
  • Lower risk of nocturnal hypoglycemia compared to NPH insulin (3 times lower incidence) 1
  • Although hypoglycemia risk increases with declining eGFR, the overall rate of severe hypoglycemia remains low 4
  • No significant changes in weight, blood pressure, or eGFR observed during treatment 3

Dosing Recommendations

Initial Dosing and Titration

• Start with a lower initial dose (typically 10 units daily) in CKD patients 3
• Titrate dose carefully based on glucose monitoring:
  • Upward or downward titration to maintain fasting plasma glucose between 90-130 mg/dL 3
  • Higher doses may be needed in advanced CKD stages (median dose increases from 44 units in CKD stage 1 to 55 units in CKD stage 4) 4

Monitoring Requirements

• More frequent blood glucose monitoring is essential in CKD patients
• Close monitoring for hypoglycemia, particularly in advanced CKD stages 2
• Regular assessment of kidney function (eGFR) to guide dose adjustments 5

Comparative Efficacy with Other Agents

Preferred Medication Hierarchy in CKD

1. GLP-1 receptor agonists (first-line for CKD patients with T2D)

   • Effective regardless of kidney function with low hypoglycemia risk 2
   • Semaglutide, liraglutide, and dulaglutide show beneficial effects on CKD progression 2

2. SGLT2 inhibitors (can be initiated if eGFR >20 mL/min/1.73m²)

   • Beneficial effects on slowing CKD progression 2
   • Glucose-lowering efficacy decreases when eGFR <45 mL/min/1.73m² 2

3. Insulin therapy (including glargine)

   • Essential option when other agents are contraindicated, not tolerated, or insufficient 2
   • Particularly important in advanced CKD (eGFR <30 mL/min/1.73m²) when other options are limited 2

Insulin Glargine vs. Other Insulins

• Insulin glargine demonstrated superior outcomes compared to NPH insulin:
  • Better HbA1c reduction (-0.91% with glargine vs. +0.23% with NPH) 1
  • Significantly fewer nocturnal hypoglycemic episodes 1
  • More stable glucose profile without pronounced peaks 1

Clinical Pitfalls and Caveats

Hypoglycemia Risk

• Approximately 33.7% of CKD patients on insulin glargine may experience documented hypoglycemia 3
• About 28.2% of hypoglycemic episodes may be severe, and 25% may be nocturnal 3
• Risk increases with declining kidney function, requiring vigilant monitoring 4

Special Considerations

• Patients with CKD and diabetes have significantly higher cardiovascular risk (87% higher risk of composite cardiovascular outcomes) 6
• Insulin glargine U300 may be particularly beneficial in advanced CKD stages due to its more stable pharmacokinetic profile 7
• Education on hypoglycemia recognition and management is critical for CKD patients on insulin 2

In conclusion, insulin glargine plays an important role in the management of diabetes in CKD patients, particularly when other agents are contraindicated or insufficient. Its favorable safety profile regarding nocturnal hypoglycemia makes it a preferred insulin option for this high-risk population, though careful dose adjustment and monitoring are essential.