What are the recommended medications for a patient with diabetes and stage 3 Chronic Kidney Disease (CKD)?

Recommended Medications for Diabetes with Stage 3 CKD

For patients with diabetes and stage 3 CKD, first-line treatment should include metformin and an SGLT2 inhibitor, with GLP-1 receptor agonists as the preferred add-on therapy when additional glycemic control is needed. 1

First-Line Therapy

Metformin

• Recommended for patients with T2D, CKD, and eGFR ≥30 ml/min/1.73 m² 1
• Dosing adjustments based on eGFR:
  • eGFR 45-59 ml/min/1.73 m²: Consider dose reduction in certain conditions 1
  • eGFR 30-44 ml/min/1.73 m²: Reduce to half the maximum dose 1
  • eGFR <30 ml/min/1.73 m²: Discontinue or do not initiate 1
• Monitor kidney function more frequently when eGFR <60 ml/min/1.73 m² 1
• Monitor vitamin B12 levels in patients on long-term metformin therapy (>4 years) 1, 2

SGLT2 Inhibitors

• Recommended for patients with T2D, CKD, and eGFR ≥30 ml/min/1.73 m² 1
• Benefits beyond glycemic control include:
  • Slowing CKD progression 1
  • Reducing heart failure risk 1
  • Cardiovascular protection 1
• Once initiated, can be continued at lower levels of eGFR 1
• Caution: Monitor for side effects including diabetic ketoacidosis, lower limb infections/amputations, and volume depletion 3

Second-Line/Add-on Therapy

GLP-1 Receptor Agonists (Preferred)

• Recommended when glycemic targets not achieved with metformin and SGLT2i 1
• Preferred over other add-on options due to:
  • Cardiovascular benefits 1
  • Weight loss benefits 1
  • Lower risk of hypoglycemia 1
• Dosing considerations:
  • Start with low dose and titrate slowly to minimize GI side effects 1
  • Select agents with documented cardiovascular benefits 1
  • Some GLP-1 RAs (e.g., dulaglutide) can be used down to eGFR >15 ml/min/1.73 m² without dose adjustment 1

Other Options (Based on Patient Factors)

DPP-4 Inhibitors

• Generally well-tolerated in CKD 1
• Low risk of hypoglycemia 1
• May be preferred in patients who want to avoid injections 1

Insulin

• Can be used at any level of kidney function, including eGFR <30 ml/min/1.73 m² and dialysis 1
• Increased risk of hypoglycemia in CKD due to decreased renal clearance 1
• May require dose reduction as kidney function declines 1

Sulfonylureas

• Use with caution due to increased risk of hypoglycemia in CKD 1
• If needed, prefer glipizide as it does not have active metabolites 1
• Avoid first-generation sulfonylureas (chlorpropamide, tolazamide, tolbutamide) 1

Thiazolidinediones (TZDs)

• Can be used in CKD without dose adjustment 1
• Consider fluid retention risk, especially with heart failure 1

Individualization Factors

• Heart Failure: Prioritize SGLT2i; avoid TZDs 1
• Established Cardiovascular Disease: Prioritize SGLT2i and GLP-1 RAs with proven CV benefits 1
• Weight Management: Prefer GLP-1 RAs and SGLT2i; avoid insulin and TZDs 1
• Hypoglycemia Risk: Avoid sulfonylureas; prefer DPP-4i, GLP-1 RAs, SGLT2i 1
• Cost Considerations: Metformin and sulfonylureas are lower cost options 1

Monitoring Recommendations

• Regular monitoring of kidney function (eGFR) 1
• More frequent monitoring when eGFR <60 ml/min/1.73 m² 1
• Monitor for vitamin B12 deficiency in long-term metformin users 1, 2
• Educate patients about sick day management (temporarily stopping metformin and SGLT2i during acute illness) 4
• Monitor for hypoglycemia, especially with insulin and sulfonylureas 1

Common Pitfalls to Avoid

• Continuing metformin at full dose when eGFR <45 ml/min/1.73 m² - Reduce dose to minimize risk of lactic acidosis 1, 5
• Failing to discontinue metformin during acute illness - Temporarily stop during conditions that increase risk of lactic acidosis (severe infection, dehydration, surgery) 4
• Overlooking cardiovascular benefits of newer agents - SGLT2i and GLP-1 RAs provide mortality benefits beyond glycemic control 1, 6
• Not adjusting insulin doses with declining kidney function - Insulin clearance decreases with CKD, increasing hypoglycemia risk 1
• Ignoring vitamin B12 monitoring - Long-term metformin use increases risk of deficiency 1, 2