What is the recommended dosing and administration of biphasic isophane insulin (Humulin M3 or Novomix) for diabetes management?

Dosing and Administration of Biphasic Isophane Insulin for Diabetes Management

Biphasic isophane insulin (Humulin M3 or NovoMix) should be administered twice daily, typically before breakfast and dinner, starting at 10 units per dose or 0.1-0.2 units/kg/day, with dose adjustments of 10-15% (or 2-4 units) once or twice weekly until target blood glucose levels are achieved. 1

Initial Dosing Recommendations

• Starting dose:
  • 10 units per dose, or
  • 0.1-0.2 units/kg of body weight per day, divided into two doses 1
• Administration timing: Before breakfast and dinner (typically twice daily) 1, 2
• Titration: Increase dose by 10-15% (or 2-4 units) once or twice weekly until fasting blood glucose target is met 1

Types of Biphasic Insulin Preparations

Biphasic insulins contain fixed proportions of rapid/short-acting and intermediate-acting insulin components:

• Humulin M3: 30% soluble regular insulin and 70% isophane insulin (NPH)
• NovoMix 30: 30% insulin aspart and 70% protaminated insulin aspart
• NovoMix 50: 50% insulin aspart and 50% protaminated insulin aspart
• NovoMix 70: 70% insulin aspart and 30% protaminated insulin aspart 3
• Lispro mixes: 25/75,50/50 formulations (25% or 50% insulin lispro with remaining portion as protaminated lispro) 1, 4

Advantages and Clinical Applications

Biphasic insulins offer several advantages:

• Target both fasting and postprandial hyperglycemia with a single injection 2
• Convenient premixed formulation improving patient adherence 2, 4
• Suitable for patients who need both basal and prandial insulin but prefer fewer daily injections 4

Special Situations

For Patients on Enteral Nutrition

• UK guidelines suggest using 70/30 mixed insulin, with half the dose at the start of the feed and half halfway through the feed 1

For Patients on Glucocorticoids

• For dexamethasone-induced hyperglycemia: Consider isophane insulin twice daily at a total dose of 0.3 units/kg/day
• Distribution: 2/3 of total daily dose in the morning and 1/3 in early evening 1

Intensification Options

If glycemic targets are not achieved with twice-daily biphasic insulin:

1. Increase to three daily injections: Add a third injection before lunch 1, 3
2. Consider higher ratio of rapid-acting component: Switch to NovoMix 50 or 70/30 lispro mix for better postprandial control 1, 3

Monitoring and Adjustment

• Adjust doses based on self-monitoring of blood glucose (SMBG) levels 1
• Target both fasting and postprandial glucose levels
• Monitor for hypoglycemia, especially when increasing doses

Common Pitfalls and Limitations

1. Fixed meal schedule requirement: Biphasic insulins work best with consistent meal timing and carbohydrate content 1
2. Less flexibility: Compared to basal-bolus regimens, premixed insulins offer less flexibility for variable meal patterns 2
3. Hypoglycemia risk: Risk of hypoglycemia is higher than with basal insulin alone but comparable to human insulin 70/30 4, 5
4. Weight gain: Mean weight gain of 4.7 kg has been observed after one year of biphasic insulin therapy 5

Comparative Efficacy

Research shows that biphasic insulin regimens:

• Provide better postprandial glucose control than basal insulin alone 6
• Result in more patients achieving target HbA1c compared to basal insulin alone (17% vs 8.1% reaching HbA1c ≤6.5%) 5
• Have similar long-term glycemic control compared to premixed human insulin in most studies 4
• Cause less hypoglycemia than prandial-only insulin regimens (5.7 vs 12.0 events per patient per year) 5

Biphasic insulin provides a practical balance between glycemic control and regimen complexity, making it particularly suitable for patients who need both basal and prandial coverage but prefer fewer daily injections.