What antidiabetic medications are suitable for patients with Chronic Kidney Disease (CKD) and diabetes?

Antidiabetic Medications for Patients with Chronic Kidney Disease

For patients with diabetes and chronic kidney disease (CKD), first-line therapy should include metformin and a sodium-glucose cotransporter-2 inhibitor (SGLT2i) for those with eGFR ≥30 ml/min per 1.73 m², with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as preferred add-on therapy when glycemic targets are not achieved. 1

First-Line Therapy Based on eGFR

Metformin

• eGFR ≥60 ml/min/1.73 m²: Full dose (up to 2000 mg daily)
• eGFR 45-59 ml/min/1.73 m²: Consider dose reduction in some patients
• eGFR 30-44 ml/min/1.73 m²: Maximum 1000 mg daily (half the maximum dose)
• eGFR <30 ml/min/1.73 m²: Contraindicated - discontinue 2

SGLT2 Inhibitors

• eGFR ≥20 ml/min/1.73 m²: Initiate therapy
• eGFR <30 ml/min/1.73 m²: Do not initiate but can continue if already started
• Dialysis: Discontinue 1

Add-on Therapy Options

When glycemic targets are not achieved with metformin and SGLT2i, or when these medications cannot be used:

1. GLP-1 Receptor Agonists (preferred) 1

   • Beneficial effects on cardiovascular outcomes
   • Potential to prevent macroalbuminuria or reduction in eGFR decline
   • Can be used in patients with reduced eGFR

2. Other options based on patient factors:

   • DPP-4 inhibitors: Can be used with dose adjustment in CKD
   • Insulin: Can be used across all stages of CKD, including dialysis
   • Sulfonylureas: Use with caution due to increased hypoglycemia risk; prefer glipizide which doesn't have active metabolites 1
   • Thiazolidinediones (TZDs): Use with caution due to fluid retention risk
   • Alpha-glucosidase inhibitors: Limited use in advanced CKD 3

Algorithm for Medication Selection Based on CKD Stage

CKD Stage 1-3a (eGFR ≥45 ml/min/1.73 m²)

1. Metformin (standard or adjusted dose) + SGLT2i
2. Add GLP-1 RA if glycemic targets not achieved
3. Consider DPP-4 inhibitors, TZDs, or sulfonylureas as third-line options

CKD Stage 3b (eGFR 30-44 ml/min/1.73 m²)

1. Metformin (reduced dose to maximum 1000 mg/day) + SGLT2i
2. Add GLP-1 RA if glycemic targets not achieved
3. Consider DPP-4 inhibitors (with dose adjustment) or insulin as third-line options

CKD Stage 4-5 (eGFR <30 ml/min/1.73 m²) or Dialysis

1. Discontinue metformin
2. Discontinue SGLT2i if not already on it (can continue if already initiated until dialysis)
3. GLP-1 RA (selected agents) and/or insulin as primary therapy
4. Consider DPP-4 inhibitors with appropriate dose adjustment

Important Considerations and Monitoring

• Hypoglycemia risk: Increases with declining kidney function, especially with insulin and sulfonylureas 1
• Metformin monitoring: Check eGFR at least annually, increasing to every 3-6 months when eGFR <60 ml/min/1.73 m² 2
• Sick day management: Discontinue metformin during acute illness, hospitalization, or procedures with contrast dye 4
• Cardiovascular protection: SGLT2i and GLP-1 RAs offer cardiovascular benefits beyond glycemic control 1
• Comprehensive approach: Include blood pressure control with ACE inhibitors or ARBs (especially with albuminuria), lipid management with statins, and lifestyle modifications 1

Lifestyle Modifications

• Diet: High in vegetables, fruits, whole grains, fiber, legumes, plant-based proteins
• Protein intake: 0.8 g/kg/day for non-dialysis patients; 1.0-1.2 g/kg/day for dialysis patients
• Sodium: Limit to <2 g/day
• Physical activity: At least 150 minutes of moderate-intensity activity per week
• Weight management: Weight loss recommended for patients with obesity, particularly with eGFR ≥30 ml/min/1.73 m² 1, 2

By following this evidence-based approach to medication selection and monitoring, patients with diabetes and CKD can achieve optimal glycemic control while minimizing risks and potentially slowing CKD progression.