What is the optimal treatment for diabetic nephropathy with preserved kidney function and mildly elevated glucose?

Treatment for Diabetic Nephropathy with Preserved Kidney Function

For patients with diabetic nephropathy and preserved kidney function (eGFR >60 ml/min/1.73m²), first-line treatment should include metformin and an SGLT2 inhibitor, with the addition of a GLP-1 receptor agonist if glycemic targets are not achieved. 1

Pharmacological Management

First-Line Therapy

• Metformin is recommended as first-line therapy for patients with diabetic nephropathy and eGFR ≥30 ml/min/1.73m² due to its effectiveness, safety, and low cost 1
• SGLT2 inhibitors should be used concurrently with metformin as first-line therapy, as they provide significant cardiorenal protection independent of their glucose-lowering effects 1
• For patients with eGFR <45 ml/min/1.73m², metformin dose should be reduced; it should be discontinued if eGFR falls below 30 ml/min/1.73m² 1, 2

Second-Line Therapy

• If glycemic targets are not achieved with metformin and an SGLT2 inhibitor, a GLP-1 receptor agonist should be added, particularly for patients with high cardiovascular risk 1
• GLP-1 receptor agonists with proven cardiovascular benefits (liraglutide, semaglutide, dulaglutide) are preferred and can be used with eGFR as low as 15 ml/min/1.73m² 1
• Common side effects of GLP-1 receptor agonists include nausea, vomiting, and diarrhea, which typically improve with dose titration 1

Lifestyle Modifications

Dietary Recommendations

• Sodium intake should be limited to <2g per day (or <5g sodium chloride) to help manage blood pressure and reduce cardiovascular risk 1
• A balanced diet high in vegetables, fruits, whole grains, fiber, and plant-based proteins is recommended, with limited processed foods and refined carbohydrates 3

Physical Activity

• Patients should undertake moderate-intensity physical activity for at least 150 minutes per week, adjusted to their cardiovascular and physical tolerance 1
• Sedentary behavior should be avoided, as physical inactivity is associated with adverse outcomes in diabetic nephropathy 1
• For patients at higher risk of falls, the intensity and type of exercise should be appropriately modified 1

Weight Management

• Weight loss is recommended for patients with obesity, particularly those with eGFR ≥30 ml/min/1.73m², as it may improve both insulin sensitivity and kidney function 1, 3

Monitoring and Follow-up

Glycemic Monitoring

• HbA1c should be used as the primary tool for monitoring glycemic control, with individualized targets ranging from <6.5% to <8.0% based on hypoglycemia risk and comorbidities 3
• More frequent monitoring of kidney function is recommended when eGFR is <60 ml/min/1.73m² 1, 3

Medication Adjustments

• As kidney function declines, medication doses and choices may need adjustment 1, 2
• If eGFR falls below 30 ml/min/1.73m², metformin should be discontinued and alternative agents considered 1, 2

Clinical Pearls and Pitfalls

• Avoid using metformin in patients at risk for acute kidney injury or dehydration, as this increases the risk of lactic acidosis 2
• Be vigilant for hypoglycemia when using insulin or insulin secretagogues, particularly as kidney function declines 1, 3
• Consider cultural differences, food intolerances, resources, and comorbidities when recommending dietary changes 1
• Engage registered dietitians, diabetes educators, or other health workers in the multidisciplinary care of patients with diabetic nephropathy 1