Treatment of Type 2 Diabetes in End-Stage Renal Disease on Peritoneal Dialysis
For patients with type 2 diabetes on peritoneal dialysis (eGFR <15 mL/min/1.73 m² or dialysis-dependent), insulin is the primary glucose-lowering agent, with GLP-1 receptor agonists as the preferred alternative when insulin alone is insufficient or when weight loss and reduced hypoglycemia risk are priorities. 1
First-Line Therapy: Insulin
Insulin remains the cornerstone of diabetes management in dialysis patients because metformin and SGLT2 inhibitors must be discontinued when eGFR falls below 30 mL/min/1.73 m². 1
Intraperitoneal insulin administration via dialysate is an option unique to peritoneal dialysis patients, mimicking physiological insulin delivery by avoiding peripheral hyperinsulinemia, though it typically requires 30-50% higher daily doses than subcutaneous routes. 2, 3
Subcutaneous insulin remains the standard approach for most patients due to simpler dosing, lower peritonitis risk, and avoidance of subcapsular hepatic steatosis associated with intraperitoneal delivery. 2
Hypoglycemia risk is substantially elevated in dialysis patients due to decreased insulin clearance, impaired gluconeogenesis, and glucose removal during exchanges—requiring frequent glucose monitoring (before and after exchanges) and conservative glycemic targets (HbA1c 7-8% rather than <7%). 2, 3
Preferred Add-On or Alternative: GLP-1 Receptor Agonists
GLP-1 receptor agonists (semaglutide, dulaglutide, liraglutide) are the preferred non-insulin agents for dialysis patients because they require no renal dose adjustment, carry minimal hypoglycemia risk when used without sulfonylureas, promote weight loss, and provide cardiovascular protection. 1, 4
These agents can be used as monotherapy in patients with residual beta-cell function or combined with insulin to reduce insulin doses and hypoglycemia frequency. 4
All long-acting GLP-1 receptor agonists are safe across all CKD stages, including dialysis, with no dose modification required. 4
Alternative Agents When GLP-1 Receptor Agonists Are Unavailable
| Agent | Renal Safety in Dialysis | Clinical Role | Key Limitations |
|---|---|---|---|
| DPP-4 inhibitors (linagliptin preferred) | Linagliptin requires no dose adjustment; others need reduction [4] | Modest glucose lowering with low hypoglycemia risk [1] | Neutral cardiovascular effect; less potent than GLP-1 RAs [1] |
| Thiazolidinediones (pioglitazone) | No dose adjustment needed [4] | Improves insulin sensitivity [1] | Fluid retention, heart failure risk, contraindicated in volume-overloaded dialysis patients [4] |
| Sulfonylureas | Require dose reduction; high hypoglycemia risk [1] | Low cost only [1] | No cardiovascular/renal protection; should be avoided [1,4] |
Agents That Must Be Discontinued
Metformin must be stopped when eGFR <30 mL/min/1.73 m² due to lactic acidosis risk; it is absolutely contraindicated in dialysis patients. 1
SGLT2 inhibitors (dapagliflozin, empagliflozin, canagliflozin) should not be initiated in dialysis patients (eGFR <20 mL/min/1.73 m²), though they may be continued if already established before dialysis initiation for residual cardiorenal protection. 1, 4
Critical Peritoneal Dialysis-Specific Considerations
Glucose absorption from dialysate (100-200 g/day) significantly worsens hyperglycemia and insulin resistance, necessitating higher insulin doses and consideration of icodextrin-based (glucose-polymer) or amino acid-based solutions to reduce glucose load. 3, 5
Icodextrin solutions contain maltose metabolites that falsely elevate glucose readings on glucose dehydrogenase-based meters (common reagent strips), causing dangerous under-treatment of true hypoglycemia—always use glucose oxidase-based meters in patients using icodextrin. 6
Protein and amino acid losses in dialysate (5-15 g/day) worsen malnutrition, requiring dietary protein intake of 1.2-1.5 g/kg/day (higher than the 0.8 g/kg/day for non-dialysis CKD). 1, 3
Glycemic Targets and Monitoring
Target HbA1c of 7-8% (rather than <7%) is appropriate for dialysis patients to balance microvascular protection against hypoglycemia risk, which carries higher mortality in this population. 2, 3
Monitor glucose before and after dialysis exchanges (at minimum 4 times daily) because glucose removal during exchanges and absorption from dialysate create unpredictable glycemic fluctuations. 2, 3
Continuous glucose monitoring is particularly valuable in dialysis patients to detect nocturnal hypoglycemia and post-exchange hyperglycemia that capillary testing misses. 3
Common Pitfalls to Avoid
Do not continue metformin or initiate SGLT2 inhibitors in dialysis patients—these are absolute contraindications at eGFR <30 and <20 mL/min/1.73 m², respectively. 1, 4
Do not use glucose dehydrogenase-based glucose meters in patients on icodextrin dialysate—maltose cross-reactivity causes falsely elevated readings that mask true hypoglycemia. 6
Do not target HbA1c <7% in dialysis patients—the hypoglycemia risk outweighs marginal microvascular benefit, and survival data favor more liberal targets (7-8%). 2, 3
Do not prescribe sulfonylureas as routine therapy—their high hypoglycemia risk, lack of cardiovascular protection, and availability of safer alternatives (GLP-1 RAs, DPP-4 inhibitors) make them inappropriate except when cost is prohibitive. 1, 4
Do not overlook cardiovascular risk factor management—ACE inhibitors or ARBs (if tolerated despite dialysis), statins, and antiplatelet therapy remain essential because cardiovascular disease is the leading cause of death in diabetic dialysis patients. 7