How to manage a patient with Type 2 diabetes mellitus (T2DM) and Chronic Kidney Disease (CKD) Stage V?

Management of Type 2 Diabetes Mellitus with CKD Stage V

In CKD Stage V (eGFR <15 mL/min/1.73 m²), insulin is the primary glucose-lowering agent, with metformin absolutely contraindicated and most oral agents either ineffective or unsafe at this level of renal function. 1, 2

Glycemic Monitoring in CKD Stage V

• Do not rely on HbA1c alone for glycemic assessment in CKD Stage V, as accuracy and precision decline substantially in advanced CKD (G4-G5), particularly among dialysis patients where HbA1c measurements have low reliability. 3, 2

• Use continuous glucose monitoring (CGM) or frequent self-monitoring of blood glucose (SMBG) to prevent hypoglycemia and guide therapy, as glucose management indicators (GMI) derived from CGM can index glycemia when HbA1c is not concordant with directly measured glucose levels. 3, 2

• Monitor glycemic control at least twice daily initially (before breakfast and bedtime) when using insulin or other agents associated with hypoglycemia risk. 1

First-Line Pharmacologic Management: Insulin

Insulin is the preferred and most effective agent for CKD Stage V, providing glucose control without the contraindications that limit oral agents at this level of renal function. 1, 2

Insulin Dosing Adjustments

• Reduce total daily insulin dose by approximately 50% compared to patients with normal renal function due to decreased renal insulin clearance and impaired renal gluconeogenesis. 2

• Start basal insulin (NPH, glargine, or detemir) at 10 units once daily at bedtime or 0.1-0.2 units/kg/day. 1

• Increase basal insulin by 2-4 units every 3 days based on fasting glucose readings, targeting fasting glucose of 80-130 mg/dL. 1

Critical Hypoglycemia Risk

• Patients with substantial decreases in eGFR have a 5-fold increase in severe hypoglycemia frequency, requiring intensive monitoring at each visit. 1, 2

• Assess for hypoglycemia symptoms at every encounter, as insulin clearance is markedly reduced in CKD Stage V. 1

Medications That Are CONTRAINDICATED in CKD Stage V

Metformin: Absolute Contraindication

• Metformin is absolutely contraindicated at eGFR <30 mL/min/1.73 m² due to lactic acidosis risk and should be discontinued immediately in CKD Stage V. 3, 1, 2

• KDIGO guidelines recommend metformin only for eGFR ≥30 mL/min/1.73 m², making it completely inappropriate for Stage V CKD. 2

SGLT2 Inhibitors: Limited Utility

• While SGLT2 inhibitors can be continued even when eGFR falls below 30 mL/min/1.73 m² if kidney replacement therapy is not imminent, their glucose-lowering efficacy is lost at eGFR <25 mL/min/1.73 m². 3, 4

• In CKD Stage V, SGLT2 inhibitors provide no meaningful glycemic control and are generally not recommended for initiation. 3, 2

GLP-1 Receptor Agonists: Variable Safety

• Most GLP-1 receptor agonists have been studied down to eGFR 15 mL/min/1.73 m², but their efficacy for glycemic control in Stage V CKD is insufficient as monotherapy. 3

• Avoid once-weekly exenatide formulation in CKD Stage V; other long-acting GLP-1 RAs (dulaglutide, liraglutide, semaglutide) require no dose adjustment but are unlikely to achieve glycemic targets alone. 3, 1

Second-Line Oral Agents: Use With Extreme Caution

Sulfonylureas: High-Risk Option

• Never use glyburide or first-generation sulfonylureas at any level of renal impairment due to accumulation of active metabolites. 3, 2

• Glipizide is the only acceptable sulfonylurea in CKD Stage V if absolutely necessary, as it lacks active metabolites that accumulate. 2

• Start glipizide conservatively at 2.5 mg once daily and titrate slowly with intensive hypoglycemia monitoring. 3, 2

• Temporarily discontinue or reduce sulfonylurea doses during acute illness, surgery, or when using nephrotoxic agents. 2

DPP-4 Inhibitors: Require Dose Adjustment

• Linagliptin requires no dose adjustment and can be used across all stages of renal impairment. 3

• Sitagliptin requires maximum dose of 25 mg once daily in CKD Stage V. 3

• Saxagliptin requires maximum dose of 2.5 mg daily in CKD Stage V. 3

• Alogliptin requires maximum dose of 6.25 mg daily in CKD Stage V. 3

• DPP-4 inhibitors are insufficient for achieving glycemic control when A1c is markedly elevated (maximum A1c reduction only 0.4-0.9%), making them inadequate as primary therapy in poorly controlled diabetes. 1

Comprehensive Management Beyond Glycemic Control

Lifestyle Modifications

• Implement structured self-management educational programs tailored to individual preferences and learning styles, as these improve biochemical outcomes (HbA1c, fasting glucose) and clinical outcomes (body weight, psychosocial measures). 3

• Recommend moderate-intensity physical activity for cumulative duration of at least 150 minutes per week, counseling patients to avoid sedentary behavior. 3

• Limit sodium intake to less than 2 g/day (or <5 g of sodium chloride) to address sodium retention that occurs with declining kidney function. 3

Cardiovascular and Renal Protection

• Advise all patients who use tobacco to quit using tobacco products, as this is a strong recommendation for diabetes and CKD management. 3

• Implement team-based, integrated care focused on risk evaluation and patient empowerment to provide comprehensive management of multiple risk factors. 3

Monitoring Schedule

• Check HbA1c every 3 months to assess response to therapy, recognizing its limitations in CKD Stage V. 3, 1

• Monitor eGFR and potassium given advanced CKD, particularly if considering any residual use of RAS inhibitors or other agents affecting electrolytes. 1

• Assess volume status regularly, as fluid management becomes critical in CKD Stage V. 3

Common Pitfalls to Avoid

• Never continue metformin in CKD Stage V under any circumstances due to prohibitive lactic acidosis risk. 2

• Do not add sulfonylureas (except glipizide with extreme caution) in advanced CKD, as these agents carry high hypoglycemia risk due to accumulation of active metabolites with reduced renal clearance. 1, 2

• Do not use HbA1c as the sole measure of glycemic control in dialysis patients; supplement with CGM or frequent SMBG. 3, 2

• Do not use standard insulin dosing without accounting for the 50% dose reduction required in CKD Stage V. 2

• Avoid acarbose and miglitol in CKD Stage V, as use is not recommended at eGFR <25 mL/min/1.73 m². 3