How do I initiate insulin therapy in a patient with Type 2 diabetes mellitus (T2DM) and diabetic chronic kidney disease (CKD)?

Initiating Insulin Therapy in Type 2 Diabetes with Diabetic Chronic Kidney Disease

For patients with Type 2 diabetes mellitus and diabetic chronic kidney disease, a GLP-1 receptor agonist is preferred over insulin, but when insulin is necessary, start with basal insulin at 10 units daily or 0.1-0.2 units/kg/day, adjusting based on kidney function and monitoring for hypoglycemia. 1

Initial Assessment and Treatment Approach

• Before initiating insulin, assess the patient's current glycemic control, kidney function (eGFR), and presence of other diabetes complications 1
• Consider insulin therapy regardless of background glucose-lowering therapy if there is evidence of ongoing catabolism (unexpected weight loss), symptoms of hyperglycemia, or when A1C >10% or blood glucose ≥300 mg/dL 1
• For patients with T2DM and CKD, the recommended treatment algorithm includes:
  • First-line therapy: Metformin (if eGFR ≥30 ml/min/1.73 m²) and SGLT2 inhibitor (if eGFR ≥20 ml/min/1.73 m²) 1
  • Additional therapy: GLP-1 receptor agonist is preferred before initiating insulin, especially in CKD 1

Insulin Initiation Protocol for T2DM with CKD

Starting Dose

• Begin with basal insulin at 10 units daily or 0.1-0.2 units/kg/day, depending on the degree of hyperglycemia 1, 2
• Administer subcutaneously into the abdominal area, thigh, or deltoid once daily at the same time every day 2
• For patients with eGFR <30 ml/min/1.73 m², consider starting at the lower end of the dosing range due to increased risk of hypoglycemia 1, 3

Insulin Selection

• Long-acting insulin analogs (glargine, detemir, degludec) are preferred over NPH insulin due to lower risk of hypoglycemia 1, 4
• Second-generation basal insulin analogs have demonstrated comparable efficacy to first-generation analogs in reducing HbA1c levels but with less hypoglycemia in patients with reduced renal function 4

Titration and Monitoring

• Adjust insulin dose based on fasting blood glucose (FBG) targets of 90-130 mg/dL 1, 5
• Increase monitoring frequency when eGFR <60 ml/min/1.73 m² 1
• Monitor for signs of overbasalization (basal dose exceeding 0.5 units/kg/day, significant bedtime-to-morning glucose differential, hypoglycemia) 1
• Consider equipping patients with an algorithm for self-titration of insulin doses based on self-monitoring of blood glucose 1

Combination Therapy Considerations

• When initiating insulin, continue metformin if eGFR ≥30 ml/min/1.73 m² 1
• Continue SGLT2 inhibitor with insulin if eGFR ≥20 ml/min/1.73 m² for cardiorenal protection 1
• If using sulfonylureas, discontinue or reduce dose when starting insulin to minimize hypoglycemia risk 1
• Consider combination therapy with GLP-1 RA and insulin for greater glycemic effectiveness and beneficial effects on weight and hypoglycemia risk 1, 6

Progression of Insulin Therapy

• If basal insulin alone doesn't achieve glycemic targets despite adequate titration:
  • Add a rapid-acting insulin analog before the meal that leads to the highest post-meal glucose excursions 7
  • Further boluses can be added at other meal times as necessary when post-meal glucose values remain above target 7
  • This stepwise strategy may eventually lead to a standard basal-bolus regimen with 3 pre-meal injections of rapid-acting insulin analogs 7

Special Considerations for CKD

• Patients with CKD are at increased risk for hypoglycemia due to decreased insulin clearance and impaired renal gluconeogenesis 3, 4
• In a study of insulin glargine in T2DM with Stage 3-4 CKD, 33.68% of patients experienced hypoglycemia, with 28.2% having severe episodes 3
• Monitor kidney function regularly and adjust insulin dose as eGFR changes 1
• For patients on dialysis, insulin requirements may decrease due to improved insulin sensitivity 1

Common Pitfalls and Caveats

• Avoid delaying insulin initiation when indicated, as therapeutic inertia can lead to prolonged hyperglycemia 1
• Be cautious about insulin-induced hypoglycemia, which is more common and potentially more severe in CKD 3, 4
• Recognize that insulin needs may change with progression of CKD or initiation of dialysis 1
• Consider cost and access issues when selecting insulin formulations 1
• Rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis 2, 5

By following this structured approach to insulin initiation in patients with T2DM and CKD, you can achieve better glycemic control while minimizing the risks of hypoglycemia and other complications.