What are kidney-friendly medications for diabetes aside from Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors?

Kidney-Friendly Medications for Diabetes Beyond SGLT2 Inhibitors

For patients with diabetes and chronic kidney disease (CKD), GLP-1 receptor agonists are the preferred kidney-friendly medication option beyond SGLT2 inhibitors, particularly long-acting formulations with proven cardiovascular benefits. 1

First-Line Treatment Approach

When managing diabetes in patients with CKD, the treatment algorithm should follow this hierarchy:

1. Metformin (if eGFR ≥30 mL/min/1.73 m²)
2. SGLT2 inhibitor (if eGFR ≥20 mL/min/1.73 m²)
3. Additional agents as needed for glycemic control

GLP-1 Receptor Agonists (First Choice Beyond SGLT2i)

GLP-1 receptor agonists are strongly recommended as the next option when:

• Patients haven't achieved glycemic targets with metformin and SGLT2i
• Patients cannot use metformin or SGLT2i
• Additional glycemic control is needed 1

Key benefits:

• Reduce albuminuria and slow eGFR decline
• Provide cardiovascular benefits (reduced MACE)
• Greater cardiovascular benefit in patients with eGFR <60 mL/min/1.73 m² 1
• Do not require dose adjustment in most cases of renal impairment

GLP-1 RA options by renal function:

• Dulaglutide, liraglutide, semaglutide: No dose adjustment required at any level of renal function
• Exenatide: Use with caution when eGFR 30-59 mL/min/1.73 m²; avoid when <30
• Lixisenatide: No adjustment for mild-moderate CKD; not recommended when eGFR <30 1

Other Kidney-Friendly Options

DPP-4 Inhibitors

• Safe in CKD with appropriate dose adjustments
• Minimal hypoglycemia risk
• Dose adjustments needed for most (except linagliptin) when eGFR <45 mL/min/1.73 m² 1

Pioglitazone (Thiazolidinedione)

• No dose adjustment required at any level of renal function
• Can be used even in advanced CKD and dialysis 2
• Benefits for cardiovascular risk reduction
• Caution: Monitor for fluid retention, heart failure risk, and fracture risk

Insulin

• Can be used at all stages of CKD
• Requires conservative initiation and careful titration to avoid hypoglycemia
• Dose requirements often decrease as kidney function declines 1

Medications to Use with Caution or Avoid

Sulfonylureas

• Use with caution in CKD due to hypoglycemia risk
• If needed, prefer glipizide (no dose adjustment required)
• Avoid glyburide in CKD 1

Alpha-Glucosidase Inhibitors

• Acarbose and miglitol not recommended when eGFR <30 mL/min/1.73 m² 1

Monitoring Recommendations

For patients with diabetes and CKD:

• Monitor eGFR at least annually
• For eGFR <60 mL/min/1.73 m², increase monitoring frequency to every 3-6 months
• Assess albuminuria regularly
• Monitor for medication-specific adverse effects

Special Considerations

• Hypoglycemia risk: Increases with declining kidney function
• Medication clearance: Many diabetes medications have reduced clearance in CKD
• Cardiovascular risk: Prioritize agents with proven cardiovascular benefits
• Cost and access: Consider medication cost and insurance coverage when selecting therapy

By following this evidence-based approach to medication selection, patients with diabetes and CKD can achieve glycemic control while protecting kidney function and reducing cardiovascular risk.