What is the treatment for Type 2 Diabetes Mellitus (T2DM) with Chronic Kidney Disease (CKD)?

Treatment of Type 2 Diabetes Mellitus with Chronic Kidney Disease

First-line treatment for T2DM with CKD should include lifestyle therapy, metformin, and a sodium-glucose cotransporter-2 inhibitor (SGLT2i), with additional drug therapy as needed for glycemic control. 1

Comprehensive Management Approach

Glycemic Management

1. First-line pharmacotherapy:

   • Metformin: Recommended for patients with eGFR ≥30 ml/min per 1.73 m² 1

     • Dose adjustment required based on renal function:
       • eGFR ≥45 ml/min/1.73 m²: Full dose (up to 2000 mg daily)
       • eGFR 30-44 ml/min/1.73 m²: Maximum 1000 mg daily
       • eGFR <30 ml/min/1.73 m²: Discontinue 2
     • Monitor eGFR every 3-6 months when <60 ml/min/1.73 m² 1

   • SGLT2 inhibitor: Recommended for patients with eGFR ≥30 ml/min per 1.73 m² 1

     • Continue as tolerated until dialysis or transplantation is initiated
     • Provides both glycemic control and cardiorenal protection 1

2. Additional therapy as needed:

   • GLP-1 receptor agonist (preferred): Recommended when glycemic targets not achieved with metformin and SGLT2i 1
   • Other options (based on patient factors):
     • DPP-4 inhibitors: Require dose adjustment in CKD
     • Insulin: Appropriate for all stages of CKD including dialysis
     • Sulfonylureas: Use with caution due to hypoglycemia risk
     • Thiazolidinediones: Consider fluid retention risk
     • Alpha-glucosidase inhibitors 1

3. Glycemic targets:

   • Individualized HbA1c target ranging from <6.5% to <8.0% for patients not on dialysis 1
   • Monitor HbA1c twice yearly if stable, up to 4 times yearly if not at goal 2

Kidney-Protective Interventions

1. Renin-angiotensin system blockade:

   • ACE inhibitor or ARB recommended for patients with albuminuria and hypertension 1
   • Titrate to highest approved dose that is tolerated 1
   • Monitor serum creatinine and potassium levels 2

2. Novel therapies:

   • Non-steroidal mineralocorticoid receptor antagonist (ns-MRA): Consider for patients with persistent albuminuria >30 mg/g despite standard therapy 1
   • Avoid nephrotoxic medications (e.g., NSAIDs) 2

Blood Pressure Management

1. Blood pressure targets:

   • <140/90 mmHg in patients without albuminuria
   • <130/80 mmHg in patients with albuminuria 3

2. Antihypertensive therapy:

   • First-line: ACEi or ARB (if albuminuria present)
   • Add dihydropyridine calcium channel blockers and/or diuretics if needed 1

Lifestyle Modifications

1. Dietary recommendations:

   • Protein intake:

     • 0.8 g protein/kg/day for patients not on dialysis 1
     • 1.0-1.2 g protein/kg/day for patients on hemodialysis or peritoneal dialysis 1

   • Sodium intake: <2 g sodium/day (<5 g sodium chloride/day) 1

   • Dietary pattern: High in vegetables, fruits, whole grains, fiber, legumes, plant-based proteins, unsaturated fats, and nuts; lower in processed meats, refined carbohydrates, and sweetened beverages 1

2. Physical activity:

   • Moderate-intensity physical activity for at least 150 minutes per week 1
   • Adjust intensity based on cardiovascular tolerance and fall risk 1
   • Avoid sedentary behavior 1

3. Weight management:

   • Weight loss recommended for patients with obesity, particularly with eGFR ≥30 ml/min per 1.73 m² 1

Monitoring and Follow-up

1. Kidney function monitoring:

   • eGFR assessment every 3-6 months 2
   • Annual testing for urine albumin excretion 2

2. Multidisciplinary care:

   • Engage registered dietitians, diabetes educators, and other health workers in nutrition care 1
   • Consider cultural differences, food intolerances, resources, cooking skills, comorbidities, and cost when recommending dietary options 1
   • Consider referral to nephrology if GFR continues to decline or difficulties arise in managing hypertension or hyperkalemia 2

Special Considerations

• Dialysis patients:

  • Insulin is appropriate for glycemic control 1
  • Adjust protein intake to 1.0-1.2 g/kg/day 1

• Transplant recipients:

  • Treat kidney transplant recipients with T2D and eGFR ≥30 ml/min per 1.73 m² with metformin according to standard recommendations 1

Common Pitfalls to Avoid

1. Failure to adjust medication doses based on kidney function:

   • Metformin requires dose reduction at eGFR <45 ml/min/1.73 m² and discontinuation at <30 ml/min/1.73 m² 2
   • Many antidiabetic medications require dose adjustments in CKD

2. Overemphasis on glycemic control at the expense of kidney protection:

   • SGLT2i provides kidney protection independent of glucose-lowering effects 4
   • Comprehensive approach addressing multiple risk factors is essential

3. Inadequate monitoring:

   • Regular assessment of kidney function, albuminuria, and medication side effects is crucial
   • More frequent monitoring needed as kidney function declines

4. Neglecting lifestyle modifications:

   • Dietary changes, physical activity, and weight management are foundational components of treatment
   • Patient education and self-management support are essential 1