What is the best management approach for a patient with diabetes and impaired renal function?

Management of Diabetes and Kidney Injury

For patients with diabetes and impaired renal function, initiate SGLT2 inhibitors and metformin as first-line therapy when eGFR ≥30 mL/min/1.73 m², add a long-acting GLP-1 receptor agonist if glycemic targets are not met, use RAS blockade for albuminuria with hypertension, and start high-intensity statin therapy immediately for all patients. 1

First-Line Pharmacologic Strategy

SGLT2 Inhibitors (Priority #1)

• Start an SGLT2 inhibitor immediately for all patients with type 2 diabetes and CKD when eGFR ≥20 mL/min/1.73 m², as these agents reduce risks of kidney disease progression, cardiovascular events, and mortality independent of glucose-lowering effects. 1
• Continue SGLT2 inhibitors until dialysis or transplantation is initiated, even as eGFR declines below 20 mL/min/1.73 m². 1
• Common pitfall: Discontinuing SGLT2 inhibitors when eGFR falls below 30—this is incorrect, as kidney and cardiovascular benefits persist at lower eGFR levels. 1

Metformin (Priority #2)

• Initiate metformin for all patients with type 2 diabetes and eGFR ≥30 mL/min/1.73 m² as it is inexpensive, well-tolerated, and effectively lowers blood glucose. 1
• Metformin is contraindicated when eGFR <30 mL/min/1.73 m² due to increased risk of lactic acidosis from drug accumulation. 2
• Obtain eGFR at least annually in all patients taking metformin, and more frequently in elderly patients at risk for renal impairment. 2

Second-Line Therapy for Glycemic Control

GLP-1 Receptor Agonists

• Add a long-acting GLP-1 receptor agonist (dulaglutide, semaglutide, or liraglutide) when metformin and SGLT2 inhibitors are insufficient to achieve glycemic targets or cannot be used. 1
• Prioritize agents with documented cardiovascular benefits: dulaglutide 1.5 mg weekly, semaglutide 1 mg weekly, or liraglutide 1.8 mg daily. 1
• GLP-1 receptor agonists can be used safely down to eGFR 15 mL/min/1.73 m² and provide cardiovascular protection beyond glucose lowering. 1, 3
• Start with low doses and titrate slowly to minimize gastrointestinal side effects (nausea, vomiting). 1
• Do not combine GLP-1 receptor agonists with DPP-4 inhibitors, as they work through similar mechanisms. 1

Blood Pressure Management

RAS Blockade for Albuminuria

• Initiate an ACE inhibitor or ARB immediately for patients with albuminuria (≥30 mg/g or ≥3 mg/mmol) and hypertension to slow CKD progression and reduce cardiovascular risk. 1
• Target blood pressure <130/80 mmHg, though this must be balanced against risk of hypotension in advanced CKD. 1, 4
• Monitor serum potassium every 2-4 weeks after RAS blockade initiation, then every 3 months, as hyperkalemia risk increases with declining kidney function. 3

Additional Antihypertensive Therapy

• Add dihydropyridine calcium channel blockers and/or diuretics if blood pressure remains above target despite RAS blockade. 1

Advanced Risk-Based Therapy

Nonsteroidal Mineralocorticoid Receptor Antagonists

• Consider adding a nonsteroidal MRA (finerenone) for patients with type 2 diabetes, eGFR ≥25 mL/min/1.73 m², normal serum potassium, and persistent albuminuria ≥30 mg/g despite maximum tolerated RAS inhibitor and SGLT2 inhibitor. 1
• This is most appropriate for patients at high risk of CKD progression and cardiovascular events, as demonstrated by persistent albuminuria despite standard-of-care therapies. 1
• Critical safety measure: Select only patients with consistently normal serum potassium and monitor potassium regularly after initiation to mitigate hyperkalemia risk. 1

Lipid Management

Statin Therapy

• Initiate high-intensity statin therapy immediately for all patients with diabetes and CKD, regardless of baseline LDL levels, to reduce cardiovascular risk. 1, 4, 3
• Add ezetimibe 10 mg daily if LDL remains >70 mg/dL on statin therapy. 4
• Consider PCSK9 inhibitors if LDL remains elevated despite statin plus ezetimibe. 4

Glycemic Monitoring and Targets

HbA1c Monitoring

• Use HbA1c to monitor glycemic control, measuring twice per year for stable patients or up to 4 times per year after therapy changes. 1
• Target HbA1c between 6.5% and 8.0% depending on hypoglycemia risk, with more intensive targets (closer to 6.5%) appropriate when using medications not associated with hypoglycemia (SGLT2 inhibitors, GLP-1 receptor agonists). 1
• Critical limitation: HbA1c accuracy declines with eGFR <15 mL/min/1.73 m², particularly in dialysis patients receiving erythropoietin, where shortened erythrocyte lifespan biases measurements toward falsely low values. 1

Alternative Monitoring

• Use continuous glucose monitoring (CGM) or self-monitoring of blood glucose when HbA1c is not concordant with directly measured glucose levels or clinical symptoms. 1
• CGM-derived glucose management indicator (GMI) can index glycemia for patients with unreliable HbA1c. 1

Lifestyle Interventions

Dietary Modifications

• Consume a diet 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
• Maintain protein intake at 0.8 g/kg/day for patients not on dialysis to avoid both malnutrition and excessive glomerular hyperfiltration. 1
• For hemodialysis patients, increase protein intake to 1.0-1.2 g/kg/day to offset dialysis-related protein losses and prevent malnutrition. 1, 4
• Limit sodium intake to <2 g/day (<5 g sodium chloride/day) to reduce blood pressure and slow CKD progression. 1, 3

Physical Activity

• Recommend at least 150 minutes per week of moderate-intensity physical activity, adjusted to cardiovascular and physical tolerance, as this improves cardiovascular health, glycemic control, and quality of life. 1, 4
• Counsel patients to avoid sedentary behavior. 1

Special Considerations for Advanced CKD

Dialysis Patients

• Insulin therapy becomes the cornerstone for patients on dialysis, as most oral agents have significant limitations at this stage. 4
• Target HbA1c between 7.0-7.5% for dialysis patients, balancing glycemic control against hypoglycemia risk. 4
• Consider adding a long-acting GLP-1 receptor agonist if insulin alone is insufficient, as these can be used safely down to eGFR 15 mL/min/1.73 m². 4

Medication Adjustments by eGFR

• eGFR 30-44 mL/min/1.73 m²: Continue metformin and SGLT2 inhibitors; assess benefit-risk of continuing metformin if eGFR falls below 45. 1, 2
• eGFR 20-29 mL/min/1.73 m²: Discontinue metformin; continue SGLT2 inhibitors. 1, 2
• eGFR <20 mL/min/1.73 m²: Discontinue metformin; may continue SGLT2 inhibitors until dialysis initiation. 1, 2

Monitoring Schedule

Regular Reassessment Every 3-6 Months

• eGFR and creatinine: Every 3 months for stable patients, every 2-4 weeks after medication changes. 1, 3
• HbA1c: Every 3-6 months depending on glycemic stability. 1, 4
• Lipid panel: Every 3 months initially after starting lipid therapy, then every 6 months once stable. 4
• Serum potassium: Every 2-4 weeks after RAS blockade or MRA initiation, then every 3 months. 3
• Urine albumin-creatinine ratio: Annually to assess albuminuria and treatment response. 5

Team-Based Care Approach

• Implement team-based, integrated care delivered by physicians, nurses, dieticians, pharmacists, and community workers to provide comprehensive risk evaluation and patient empowerment. 1
• Refer to nephrology when eGFR falls below 30 mL/min/1.73 m² or for complex management issues. 5, 6