What is the proposed Guideline-Directed Medical Therapy (GDMT) for patients with Chronic Kidney Disease (CKD) and Type 2 Diabetes Mellitus (T2DM)?

Guideline-Directed Medical Therapy for Patients with CKD and Type 2 Diabetes

The cornerstone of guideline-directed medical therapy (GDMT) for patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) should include metformin, SGLT2 inhibitors, RAS blockade with ACEi/ARBs, and comprehensive cardiovascular risk reduction strategies. 1

First-Line Pharmacotherapy

Glycemic Management

1. Metformin

   • Recommended for patients with T2DM and CKD with eGFR ≥30 ml/min/1.73 m² 1
   • Dosing adjustments based on eGFR:
     • 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
     • eGFR 30-44 ml/min/1.73 m²: Maximum 1000 mg daily (half maximum dose)
     • eGFR <30 ml/min/1.73 m²: Discontinue 2
   • Monitor vitamin B12 levels in patients on long-term therapy (>4 years) 2

2. SGLT2 Inhibitors

   • Recommended for patients with T2DM and CKD with eGFR ≥30 ml/min/1.73 m² 1
   • Can be initiated at eGFR ≥20 ml/min/1.73 m² and continued until dialysis or transplant 1
   • Provide cardiorenal protection beyond glycemic control 3, 4
   • Mechanisms include modulation of RAAS, increased hematocrit, altered energy substrate use, and reduced inflammation 3

Kidney Protection

1. RAS Blockade (ACEi or ARB)
   • Recommended for patients with diabetes, hypertension, and albuminuria 1
   • Titrate to the highest approved dose that is tolerated 1
   • Reduces risk of CKD progression by decreasing albuminuria and slowing eGFR decline 1
   • Monitor serum creatinine and potassium levels 2

Second-Line and Additional Therapies

1. GLP-1 Receptor Agonists

   • Recommended when glycemic targets are not achieved despite metformin and SGLT2i, or when these medications cannot be used 1
   • Provide cardiovascular benefits and potential kidney protection 1, 2
   • Can be used across a wide range of eGFR levels 2

2. Non-steroidal Mineralocorticoid Receptor Antagonists (ns-MRA)

   • Consider for patients with T2DM and CKD with albuminuria ≥30 mg/g (≥3 mg/mmol) and normal potassium levels 1
   • Finerenone has shown benefits in reducing kidney failure and cardiovascular events 1

3. Lipid Management

   • Moderate to high-intensity statin therapy based on ASCVD risk 1, 2
   • Consider ezetimibe, PCSK9 inhibitors, or icosapent ethyl for patients with elevated ASCVD risk 1

Comprehensive Risk Factor Management

1. Blood Pressure Control

   • Target individualized BP goals
   • First-line: ACEi or ARB (especially with albuminuria)
   • Add dihydropyridine calcium channel blockers and/or diuretics as needed 1
   • Consider steroidal MRA for resistant hypertension if eGFR ≥45 ml/min/1.73 m² 1

2. Antiplatelet Therapy

   • For secondary prevention in established cardiovascular disease 1
   • Consider for primary prevention in high-risk individuals, balancing bleeding risk 1

Lifestyle Modifications

1. Nutrition

   • Dietary protein intake: approximately 0.8 g/kg/day for patients not on dialysis 1
   • Increase to 1.0-1.2 g/kg/day for patients on dialysis 1, 2
   • Sodium intake: <2 g/day (<5 g sodium chloride/day) 1, 2
   • Emphasize vegetables, fruits, whole grains, fiber, legumes, plant-based proteins, unsaturated fats, and nuts 2
   • Limit processed meats, refined carbohydrates, and sweetened beverages 2

2. Physical Activity

   • Moderate-intensity physical activity for at least 150 minutes per week 1, 2
   • Avoid sedentary behavior 1, 2

3. Weight Management

   • Weight loss recommended for patients with obesity, particularly with eGFR ≥30 ml/min/1.73 m² 2

Monitoring and Follow-up

1. Kidney Function

   • Monitor eGFR at least annually in patients with normal kidney function 2
   • Increase monitoring frequency to every 3-6 months in patients with eGFR <60 ml/min/1.73 m² 2
   • Annual testing for urine albumin excretion 2

2. Glycemic Control

   • Individualized HbA1c targets ranging from <6.5% to <8.0% for patients with T2DM and CKD not on dialysis 2
   • Monitor HbA1c twice yearly if stable, up to 4 times yearly if not at goal 2

Clinical Pearls and Pitfalls

• Metformin: Discontinue during hospitalizations, serious intercurrent illness, and when acute illness may compromise renal or liver function 2
• SGLT2 Inhibitors: Monitor for genital mycotic infections, volume depletion, and diabetic ketoacidosis 3
• RAS Blockade: Watch for acute kidney injury, hyperkalemia, and angioedema (especially with ACEi) 1
• Dual RAS Blockade: Avoid combining ACEi and ARB due to increased risk of adverse events without additional benefit 1
• Comprehensive Approach: The combination of SGLT2i, metformin, and RAS blockade provides synergistic cardiorenal protection 5, 6

The prevalence of CKD among patients with T2DM is approximately 40% and continues to grow 5, 7. Early intervention with this comprehensive GDMT approach can significantly reduce the risk of CKD progression, cardiovascular events, and mortality in this high-risk population.