What are the recommended antihyperglycemic agents for a patient with End-Stage Renal Disease (ESRD) on Peritoneal Dialysis (PD) who is oliguric?

Antihyperglycemic Agents for Patients on Peritoneal Dialysis with ESRD and Oliguria

For patients with ESRD on peritoneal dialysis who are oliguric, insulin therapy is the primary recommended treatment, with DPP-4 inhibitors (particularly linagliptin) as the preferred oral agent due to their safety profile and lack of dose adjustment requirements in ESRD. 1

First-Line Therapy Options

Insulin

• Dosing considerations:
  • Reduce total daily insulin dose by 50% for patients with type 2 diabetes and ESRD 1
  • For patients with type 1 diabetes and ESRD, reduce total daily insulin dose by 35-40% 1
  • Initiate and titrate conservatively to avoid hypoglycemia 1
  • Monitor closely due to increased risk of hypoglycemia in ESRD patients on dialysis 1

DPP-4 Inhibitors

• Linagliptin: No dose adjustment required in ESRD or dialysis 1
• Sitagliptin: Reduce to 25 mg daily 1
• Alogliptin: Reduce to 6.25 mg daily 1
• Saxagliptin: Reduce to 2.5 mg daily 1

Second-Line Options

GLP-1 Receptor Agonists

• Preferred agents:
  • Dulaglutide: No dose adjustment required 1
  • Liraglutide: No dose adjustment required 1
  • Semaglutide: No dose adjustment required 1
• Avoid:
  • Exenatide: Contraindicated in ESRD 1
  • Lixisenatide: Not recommended with eGFR <15 ml/min/1.73m² 1

Sulfonylureas

• Glipizide: Can be used with caution; initiate at low dose (e.g., 2.5 mg daily) 1
• Glimepiride: Start with lower dose (1 mg daily) 1
• Avoid:
  • Glyburide: Contraindicated in ESRD 1

Meglitinides

• Repaglinide: Initiate conservatively at 0.5 mg with meals 1, 2
• Nateglinide: Initiate conservatively at 60 mg with meals 1

Medications to Avoid in ESRD on Dialysis

• Metformin: Contraindicated due to risk of lactic acidosis 1
• SGLT2 inhibitors: Not recommended for initiation in ESRD; limited efficacy in this population 1
• Alpha-glucosidase inhibitors: Generally not recommended in ESRD 1, 2

Special Considerations for Peritoneal Dialysis

1. Glucose absorption from dialysate:

   • PD patients may absorb 100-200g of glucose daily from dialysate
   • This can contribute to hyperglycemia and complicate glycemic control
   • May require higher insulin doses compared to hemodialysis patients

2. Hypoglycemia risk:

   • Higher risk due to decreased renal gluconeogenesis
   • Impaired insulin clearance by the kidney
   • Reduced insulin degradation due to uremia
   • Impaired counterregulatory hormone responses

3. Monitoring considerations:

   • HbA1c is not reliable in ESRD; consider alternative glycemic monitoring methods 1
   • More frequent blood glucose monitoring is recommended

Clinical Approach Algorithm

1. Assess current glycemic control and hypoglycemia risk

   • Review blood glucose patterns and hypoglycemic episodes
   • Consider continuous glucose monitoring if available

2. First-line therapy selection:

   • For most patients: Start with insulin therapy at reduced doses (50% reduction from standard)
   • For patients with mild hyperglycemia and preference for oral agents: Consider DPP-4 inhibitors (preferably linagliptin)

3. Titration and monitoring:

   • Adjust insulin doses based on blood glucose patterns
   • Monitor for hypoglycemia, especially during and after dialysis sessions
   • Consider adding a DPP-4 inhibitor to insulin for patients requiring multiple daily injections

4. For patients with significant insulin resistance:

   • Consider adding a GLP-1 RA (dulaglutide, liraglutide, or semaglutide)
   • These agents provide additional benefits of weight loss and reduced hypoglycemia risk

Common Pitfalls and How to Avoid Them

1. Overtreatment leading to hypoglycemia:

   • Start with lower insulin doses than typically used in non-ESRD patients
   • Perform more frequent blood glucose monitoring
   • Educate patients about hypoglycemia symptoms and management

2. Reliance on HbA1c for monitoring:

   • HbA1c is less reliable in ESRD due to reduced red blood cell lifespan
   • Use frequent blood glucose monitoring or continuous glucose monitoring when available

3. Inappropriate medication use:

   • Avoid metformin and SGLT2 inhibitors
   • Use caution with sulfonylureas due to hypoglycemia risk
   • Ensure proper dose adjustments for all medications

4. Failure to account for glucose absorption from PD fluid:

   • Consider using icodextrin-based PD solutions for the long dwell to reduce glucose absorption
   • Adjust insulin timing and dosing to account for glucose absorption patterns

By following these recommendations, clinicians can optimize glycemic control while minimizing hypoglycemia risk in patients with ESRD on peritoneal dialysis.