How to manage Humalog (insulin lispro protamine/insulin lispro) 75/25 insulin?

Management of Humalog 75/25 Insulin

For patients on Humalog 75/25 (insulin lispro protamine/insulin lispro) premixed insulin, the optimal approach is to transition to a simplified regimen with 70% of the total daily dose as basal insulin administered in the morning, while discontinuing prandial insulin and adding appropriate non-insulin agents. 1

Understanding Humalog 75/25

Humalog 75/25 is a premixed insulin containing:

• 75% insulin lispro protamine (intermediate-acting)
• 25% insulin lispro (rapid-acting)

This formulation provides both immediate glucose-lowering effects and extended coverage between meals from a single injection 2.

Simplification Algorithm for Premixed Insulin Management

Step 1: Transition to Basal Insulin Only

• Use 70% of total daily premixed insulin dose as basal insulin only
• Administer in the morning (not at bedtime)
• Choose an appropriate basal insulin (glargine U-100/U-300, detemir, degludec, or NPH) 1

Step 2: Titration Based on Fasting Glucose

• Target fasting glucose: 90-150 mg/dL (5.0-8.3 mmol/L)
• If 50% of fasting fingerstick values are above target: Increase dose by 2 units
• If >2 fasting fingerstick values/week are <80 mg/dL: Decrease dose by 2 units
• Adjust goals based on overall health and care objectives 1

Step 3: Add Non-Insulin Agents

• If eGFR ≥45 mL/min: Start metformin 500 mg daily, increasing dose every 2 weeks as tolerated
• If eGFR <45 mL/min or metformin not tolerated: Proceed to second-line agents
• Consider patient comorbidities (CKD, ASCVD, weight concerns) when selecting additional agents 1

Monitoring and Adjustment

• Check fingerstick glucose before lunch and dinner every 2 weeks
• Target premeal glucose: 90-150 mg/dL (5.0-8.3 mmol/L)
• If 50% of premeal values over 2 weeks exceed target: Increase dose or add another agent
• If >2 premeal values/week are <90 mg/dL: Decrease medication dose 1

Special Considerations for Older Adults

For older adults with type 2 diabetes on Humalog 75/25, simplification is particularly important:

• Complex/intermediate health status: Target A1C <8.0% (<64 mmol/mol)
• Very complex/poor health: Target A1C <8.5% (<69 mmol/mol)
• Consider deintensification if severe or recurrent hypoglycemia occurs
• Avoid rapid-acting insulin at bedtime 1

Temporary Sliding Scale During Transition

While adjusting from premixed to basal insulin:

• For premeal glucose >250 mg/dL: Add 2 units of short/rapid-acting insulin
• For premeal glucose >350 mg/dL: Add 4 units of short/rapid-acting insulin
• Discontinue sliding scale when no longer needed daily 1

Clinical Evidence

Research shows that Humalog 75/25 provides better postprandial glycemic control compared to human insulin 70/30, with lower postprandial glucose excursions 3. However, the current trend in diabetes management, especially for older adults, is to simplify insulin regimens to reduce hypoglycemia risk while maintaining adequate glycemic control 2.

The simplification approach outlined above aligns with the most recent guidelines from the American Diabetes Association and has been shown to reduce hypoglycemia risk while maintaining reasonable glycemic control in older adults with diabetes 1.