How do you titrate premixed insulin (e.g. Novolog Mix 70/30 (insulin aspart protamine/insulin aspart) or Humalog Mix 75/25 (insulin lispro protamine/insulin lispro))?

Titrating Premixed Insulin

For premixed insulin regimens (Novolog Mix 70/30 or Humalog Mix 75/25), titrate by adjusting the total daily dose by 2 units based on fasting glucose values, with a target fasting glucose of 90-150 mg/dL, checking values over a 1-week period. 1, 2

Initial Dosing and Administration

• Start insulin-naïve patients with 10 units or 0.1-0.2 units/kg body weight of premixed insulin, divided into two daily doses 2
• Administer twice daily: before breakfast and before dinner 2
• Unlike basal-bolus regimens, premixed insulins require consistent meal timing every day to match the fixed insulin action profile 1
• Do not skip meals when on premixed insulin to reduce hypoglycemia risk 1

Titration Algorithm

Fasting Glucose-Based Adjustments

• If 50% of fasting fingerstick glucose values are above goal (90-150 mg/dL): Increase total daily dose by 2 units 1, 2
• If >2 fasting fingerstick values per week are <80 mg/dL: Decrease total daily dose by 2 units 1, 2
• Assess fasting glucose values over a 1-week period before making dose adjustments 1

Premeal Glucose Monitoring

• After achieving fasting glucose targets, monitor premeal glucose before lunch and dinner every 2 weeks 1
• Goal: 90-150 mg/dL before meals 1
• If 50% of premeal values over 2 weeks are above goal: Increase the dose or add another glucose-lowering agent 1
• If >2 premeal values per week are <90 mg/dL: Decrease the medication dose 1

Simplified Sliding Scale During Titration

While adjusting premixed insulin doses, a simplified correction scale may be used temporarily 1:

• For premeal glucose >250 mg/dL: Give 2 units of short- or rapid-acting insulin 1
• For premeal glucose >350 mg/dL: Give 4 units of short- or rapid-acting insulin 1
• Stop the sliding scale when not needed daily 1

Critical Safety Considerations

• Do not use rapid- or short-acting insulin at bedtime to avoid nocturnal hypoglycemia 1, 2
• Always carry a source of quick-acting carbohydrates as physical activity may cause hypoglycemia depending on timing 1
• Monitor for hypoglycemia, which is the most common adverse effect, though major hypoglycemia is rare with premixed insulins 2, 3
• For any hypoglycemia: Determine the cause; if no clear reason exists, lower the corresponding dose by 10-20% 1

When Premixed Insulin Fails to Achieve Targets

If A1C remains above goal despite titration 1:

• Consider advancing to thrice-daily premixed insulin 2
• Consider switching to a basal-bolus regimen for more flexibility 2
• Consider adding a GLP-1 receptor agonist to the regimen 2

Important Limitations and Pitfalls

• Premixed insulins offer less flexibility in dose adjustment compared to separate basal and bolus insulins 2
• The fixed ratio (70/30 or 75/25) may not be optimal for patients with varying insulin requirements throughout the day 2
• Premixed insulin analogues provide superior postprandial glucose control compared to premixed human insulin, but overall A1C reduction is comparable 3, 4
• Meals must be consumed at similar times every day when using premixed insulin, unlike basal-bolus regimens which allow flexible meal timing 1