What is the appropriate schedule for splitting the total daily dose of NPH (Neutral Protamine Hagedorn) insulin?

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NPH Insulin Dosing Schedule

When splitting NPH insulin, administer 2/3 of the total daily dose before breakfast and 1/3 before dinner. 1

Standard Split-Dose Regimen

The twice-daily NPH schedule is the recommended approach when intensifying from once-daily dosing:

  • Split the total NPH dose with 2/3 administered before breakfast and 1/3 administered before dinner 1
  • When converting from bedtime-only NPH to a split regimen, reduce the total NPH dose to 80% of the current bedtime dose, then divide according to the 2/3:1/3 ratio 1
  • Add 4 units of short/rapid-acting insulin to each injection, or 10% of the reduced NPH dose, for prandial coverage 1

Initial NPH Dosing (Once-Daily)

For patients starting NPH insulin:

  • Begin with bedtime administration at 10 units per day OR 0.1-0.2 units/kg per day 1
  • Titrate by increasing 2 units every 3 days to reach fasting plasma glucose goal without hypoglycemia 1
  • If hypoglycemia occurs without clear cause, reduce the dose by 10-20% 1

When to Convert to Twice-Daily NPH

Consider splitting to twice-daily NPH when:

  • A1C remains above goal despite optimized bedtime NPH dosing 1
  • Adding prandial insulin coverage is needed 1
  • Daytime hyperglycemia persists despite dose adjustments 2

Special Clinical Scenarios

Steroid-Induced Hyperglycemia

  • Administer NPH in the morning (not split) to match the pharmacokinetic profile of daily glucocorticoid therapy 2
  • This timing aligns with the peak hyperglycemic effect of glucocorticoids, which occurs 4-6 hours after steroid administration 2

Type 1 Diabetes with Intensive Control

  • Research demonstrates that splitting evening insulin by giving regular insulin at dinner and NPH at bedtime (rather than mixing both at dinner) reduces nocturnal hypoglycemia by 64% (0.10 vs 0.28 episodes/patient-day) and improves HbA1c (7.0% vs 7.5%) 3
  • This split-evening approach is superior to administering both insulins together before dinner 3

Type 2 Diabetes

  • Bedtime NPH administration may be preferable to morning dosing in Type 2 diabetes, resulting in better fasting glucose control (4.6 vs 8.6 mmol/L) and lower HbA1c (5.81% vs 6.23%) 4
  • However, when splitting is required for intensification, use the standard 2/3 morning, 1/3 evening distribution 1

Common Pitfalls to Avoid

  • Do not give equal doses morning and evening—the 2/3:1/3 ratio accounts for greater insulin sensitivity overnight and reduces nocturnal hypoglycemia risk 1
  • Do not maintain the same total daily dose when converting from once to twice-daily—reduce to 80% of the bedtime dose first 1
  • Avoid administering both NPH and rapid-acting insulin together at dinner in Type 1 diabetes—this increases nocturnal hypoglycemia compared to separating NPH to bedtime 3
  • For patients on tube feeding requiring NPH, consider splitting into twice or three times daily to cover continuous nutritional intake 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Management of Steroid-Induced Hyperglycemia with NPH Insulin

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Morning versus bedtime isophane insulin in type 2 (non-insulin dependent) diabetes mellitus.

Diabetic medicine : a journal of the British Diabetic Association, 1992

Guideline

NPH Insulin Dose Adjustment for Increased Carbohydrate Intake

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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