What is a recommended dosing schedule for NPH (Neutral Protamine Hagedorn) insulin?

From the Guidelines

NPH insulin should be administered twice daily, with two-thirds of the total daily dose given in the morning and one-third given in the evening, starting with a dose of 10 units per day or 0.1-0.2 units/kg per day, and titrated based on individualized needs, as recommended by the most recent guidelines 1. The dosing schedule for NPH insulin can be broken down into the following key points:

• Start with a dose of 10 units per day or 0.1-0.2 units/kg per day 1
• Administer two-thirds of the total daily dose in the morning and one-third in the evening 1
• Titrate the dose based on individualized needs, with increments of 2 units every 3 days to reach the target fasting plasma glucose (FPG) goal without hypoglycemia 1
• Monitor for hypoglycemia symptoms and adjust the dose accordingly, with a reduction of 10-20% if no clear reason for hypoglycemia is found 1 The importance of individualized titration and monitoring for hypoglycemia symptoms cannot be overstated, as it allows for tailored adjustments to the insulin regimen and minimizes the risk of adverse effects. Some key considerations when initiating NPH insulin therapy include:
• Setting an FPG goal and choosing an evidence-based titration algorithm 1
• Assessing the adequacy of insulin dose at every visit and considering clinical signals to evaluate for overbasalization and the need for adjunctive therapies 1
• Being aware of the potential for hypoglycemia, particularly in the mid-morning and middle of the night, and advising patients to monitor for symptoms and maintain a consistent meal schedule 1

From the FDA Drug Label

CLINICAL STUDIES The efficacy and safety of LEVEMIR given once-daily at bedtime or twice-daily (before breakfast and at bedtime, before breakfast and with the evening meal, or at 12-hour intervals) was compared to that of once-daily or twice-daily NPH human insulin or once-daily insulin glargine in non-blinded, randomized, parallel studies of 6004 patients with diabetes (3724 with type 1, and 2280 with type 2). In one non-blinded clinical study (Study A, n=409), adult patients with type 1 diabetes were randomized to treatment with either LEVEMIR at 12-hour intervals, LEVEMIR morning and bedtime or NPH human insulin morning and bedtime. LEVEMIR-treated patients had a decrease in HbA1c similar to that of NPH human insulin In a randomized, controlled clinical study (Study C, n=749), patients with type 1 diabetes were treated with once-daily (bedtime) LEVEMIR or NPH human insulin, both in combination with human soluble insulin before each meal for 6 months. In a non-blinded, randomized, controlled clinical study (Study D, n=347), pediatric patients (age range 6 to 17) with type 1 diabetes were treated for 26 weeks with a basal-bolus insulin regimen LEVEMIR and NPH human insulin were administered once- or twice-daily (bedtime or morning and bedtime) according to pretrial dose regimen. In a 24-week, non-blinded, randomized, clinical study (Study E, n=476), LEVEMIR administered twice-daily (before breakfast and evening) was compared to a similar regimen of NPH human insulin as part of a regimen of combination therapy with one or two of the following oral antidiabetes agents (metformin, insulin secretagogue, or α–glucosidase inhibitor)

The recommended dosing schedule for NPH insulin is:

• Once-daily: at bedtime
• Twice-daily:
  • morning and bedtime
  • before breakfast and at bedtime
  • before breakfast and with the evening meal
  • at 12-hour intervals 2

From the Research

Dosing Schedule for NPH Insulin

• The recommended initial dose of NPH insulin is 10 units/day or 0.1-0.2 units/kg/day, which can be titrated based on the patient's self-measured fasting plasma glucose levels 3.
• A simple rule for titrating the dose is to gradually increase the initial dose by 1 unit per day (for NPH, insulin detemir, and glargine 100 units/mL) or 2-4 units once or twice per week (for NPH, insulin detemir, glargine 100 and 300 units/mL, and degludec) until the target fasting plasma glucose level is reached 3.
• The dose of basal insulin, including NPH, should be increased as required up to approximately 0.5-1.0 units/kg/day in some cases 3.
• For patients with type 2 diabetes, NPH insulin can be initiated at bedtime with a dose of 10 units, and titrated regularly based on fasting glucose levels 4.
• Alternatively, twice daily premixed insulin (e.g., aspart 30%/NPH 70%) can be initiated at a dose of 6-10 units twice per day, targeting daytime or postprandial hyperglycemia 4.

Administration Timing

• NPH insulin can be administered at bedtime or in the morning, depending on the patient's individual needs and glucose control goals 5, 4.
• When administered with lispro insulin, NPH can be given as a pre-meal combination to improve overall blood glucose control in type 1 diabetic patients 6.
• The timing of NPH administration can be adjusted based on the patient's lifestyle and glucose monitoring results to optimize glucose control 3, 4.