What is an alternative insulin regimen if Humalog (insulin lispro protamine/insulin lispro) 75/25 is unavailable and only Novolog (insulin aspart) or Lispro (insulin lispro) are available?

Alternative Insulin Regimen When Humalog 75/25 is Unavailable

When Humalog 75/25 is unavailable, switch to a basal-bolus regimen using available insulin lispro (Humalog) or insulin aspart (Novolog) as rapid-acting prandial insulin twice daily before breakfast and dinner, combined with NPH insulin to provide basal coverage. 1, 2

Understanding the Substitution Challenge

Humalog 75/25 is a premixed insulin containing 75% insulin lispro protamine (intermediate-acting) and 25% rapid-acting insulin lispro, designed for twice-daily administration before breakfast and dinner. 2, 3 The key challenge is that you cannot simply substitute with pure rapid-acting insulin alone—you must replicate both the basal and prandial components. 4

Recommended Substitution Strategy

Option 1: Basal-Bolus Regimen (Preferred for Flexibility)

Convert to rapid-acting insulin lispro or aspart before meals plus NPH insulin:

• Calculate the total daily dose (TDD) from the patient's current Humalog 75/25 regimen 2
• Distribute as follows:
  • Give 50% of TDD as NPH insulin (split into morning and evening doses, with 2/3 in morning and 1/3 in evening) 2, 4
  • Give 50% of TDD as rapid-acting insulin lispro or aspart (divided before breakfast and dinner) 1, 5
• Administer rapid-acting insulin 0-5 minutes before meals (this maintains the convenience of the original Humalog 75/25 timing) 5, 6

Option 2: Alternative Premixed Formulation

If Novolog 70/30 (aspart 70/30) is available, this is the closest equivalent:

• Novolog 70/30 contains 70% insulin aspart protamine and 30% rapid-acting insulin aspart 1, 7
• Use the same total daily dose as the patient's Humalog 75/25, maintaining the 2/3 morning and 1/3 evening distribution 2, 4
• This provides comparable glycemic control with similar pharmacokinetic profiles 7, 8

Critical Pharmacokinetic Considerations

Insulin lispro and insulin aspart are clinically interchangeable:

• Both have onset of action at 0.25-0.5 hours, peak at 1-3 hours, and duration of 3-5 hours 1
• Insulin aspart may have slightly more rapid absorption than lispro, but this difference is clinically insignificant for most patients 8
• Both maintain their rapid-acting properties even when used in basal-bolus regimens 3, 6

Dosing Algorithm for Conversion

Step 1: Calculate current TDD from Humalog 75/25

• Add morning + evening doses of Humalog 75/25 2

Step 2: If converting to basal-bolus:

• NPH morning dose = (TDD × 0.5) × 0.67 2, 4
• NPH evening dose = (TDD × 0.5) × 0.33 2, 4
• Rapid-acting before breakfast = (TDD × 0.5) × 0.67 5
• Rapid-acting before dinner = (TDD × 0.5) × 0.33 5

Step 3: If converting to Novolog 70/30:

• Use same TDD with 2/3 before breakfast and 1/3 before dinner 4

Essential Monitoring During Transition

Increase blood glucose monitoring frequency during the first 1-2 weeks:

• Check fasting glucose (to adjust NPH or basal component) 2, 4
• Check 2-hour postprandial glucose after breakfast and dinner (to adjust rapid-acting component) 2, 4
• Monitor for hypoglycemia, particularly overnight and pre-dinner 2, 6

Adjust doses based on patterns:

• If fasting glucose elevated: increase evening NPH by 10-20% 2
• If pre-dinner glucose elevated: increase morning NPH by 10-20% 2
• If postprandial glucose elevated: increase corresponding rapid-acting dose by 10-20% 5
• If hypoglycemia occurs: reduce the corresponding insulin component by 10-20% 2

Critical Pitfalls to Avoid

Do not use equal morning and evening doses:

• The morning dose should be approximately twice the evening dose (2/3 vs 1/3 distribution) 2, 4
• Using equal doses increases risk of nocturnal hypoglycemia 2

Do not mix insulins in the same syringe:

• Never mix rapid-acting insulin lispro or aspart with NPH in the same syringe if attempting to create a "homemade" premix 2
• The pharmacokinetics will be unpredictable and potentially dangerous 2

Emphasize meal timing consistency:

• Patients must maintain consistent meal timing when using any premixed-equivalent regimen 2, 4
• Skipping meals or significant delays increase hypoglycemia risk substantially 4

Continue metformin but discontinue sulfonylureas:

• Maintain metformin during insulin transition 5, 4
• Stop sulfonylureas to reduce hypoglycemia risk 5, 4

Advantages of Basal-Bolus Over Direct Premix Substitution

The basal-bolus approach using available lispro or aspart provides:

• Greater flexibility in meal timing and carbohydrate intake 4
• Ability to independently adjust basal vs prandial components based on glucose patterns 5
• Comparable or superior glycemic control to premixed formulations 1, 7
• Similar or lower hypoglycemia rates when properly titrated 6, 7